| 1. |
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| 2. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 3. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 4. |
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| 5. |
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| 6. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 7. |
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| 8. |
- Shrestha, R, et al.
(författare)
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Molecular pathogenesis of progression to myeloid leukemia from TET-insufficient status
- 2020
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 4:5, s. 845-854
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Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function mutations in ten-eleven translocation-2 (TET2) are recurrent events in acute myeloid leukemia (AML) as well as in preleukemic hematopoietic stem cells (HSCs) of age-related clonal hematopoiesis. TET3 mutations are infrequent in AML, but the level of TET3 expression in HSCs has been found to decline with age. We examined the impact of gradual decrease of TET function in AML development by generating mice with Tet deficiency at various degrees. Tet2f/f and Tet3f/f mice were crossed with mice expressing Mx1-Cre to generate Tet2f/wtTet3f/fMx-Cre+ (T2ΔT3), Tet2f/fTet3f/wtMx-Cre+ (ΔT2T3), and Tet2f/fTet3f/fMx-Cre+ (ΔT2ΔT3) mice. All ΔT2ΔT3 mice died of aggressive AML at a median survival of 10.7 weeks. By comparison, T2ΔT3 and ΔT2T3 mice developed AML at longer latencies, with a median survival of ∼27 weeks. Remarkably, all 9 T2ΔT3 and 8 ΔT2T3 mice with AML showed inactivation of the remaining nontargeted Tet2 or Tet3 allele, respectively, owing to exonic loss in either gene or stop-gain mutations in Tet3. Recurrent mutations other than Tet3 were not noted in any mice by whole-exome sequencing. Spontaneous inactivation of residual Tet2 or Tet3 alleles is a recurrent genetic event during the development of AML with Tet insufficiency.
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| 9. |
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| 10. |
- Ingelsson, Martin, et al.
(författare)
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Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains
- 2007
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 114:5, s. 471-479
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Tidskriftsartikel (refereegranskat)abstract
- Some cases of familial frontotemporal dementia (FTD) leading to frontotemporal lobar degeneration (FTLD) are caused by mutations in tau on chromosome 17 (FTDP-17). Certain mutations alter the ratio between four (4R tau) and three (3R tau) repeat tau isoforms whereas cases with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) mainly have 4R tau brain pathology. We assessed tau mRNA and protein levels in frontal cortex from 15 sporadic FTLD, 21 PSP, 5 CBD, 15 Alzheimer’s disease (AD) and 16 control brains. Moreover, we investigated the disease association and possible tau splicing effects of the tau H1 haplotype. Cases with FTLD and PSP had lower tau mRNA levels than control brains. When analyzing 4R tau and 3R tau mRNA separately, control subjects displayed a 4R tau/3R tau ratio of 0.48. Surprisingly, FTLD brains displayed a more elevated ratio (1.32) than PSP brains (1.12). Also, several FTLD and PSP cases had higher 4R tau/3R tau mRNA than FTDP-17 cases, included as reference tissues, and the ratio increase was seen regardless of underlying histopathology, i.e. both for tau-positive and tau-negative FTLD cases. Furthermore, total tau protein levels were slightly decreased in both FTLD and AD as compared to control subjects. Finally, we confirmed the association of tau H1 with PSP, but could not find any haplotype-related effect on tau exon 10 splicing. In conclusion, we demonstrated increased but largely variable 4R tau/3R tau mRNA ratios in FTLD and PSP cases, suggesting heterogeneous pathophysiological processes within these disorders.
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| 11. |
- Matsui, H., et al.
(författare)
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A Multi-Instrument Study of a Dipolarization Event in the Inner Magnetosphere
- 2021
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:5
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Tidskriftsartikel (refereegranskat)abstract
- A dipolarization of the background magnetic field was observed during a conjunction of the Magnetospheric Multiscale (MMS) spacecraft and Van Allen Probe B on September 22, 2018. The spacecraft were located in the inner magnetosphere at L similar to 6-7 just before midnight magnetic local time (MLT). The radial separation between MMS and Probe B was similar to 1R(E). Gradual dipolarization or an increase of the northward component B-Z of the background field occurred on a timescale of minutes. Exploration of energization and Radiation in Geospace located 0.5 MLT eastward at a similar L shell also measured a gradual increase. The spatial scale was of the order of 1 R-E. On top of that, MMS and Probe B measured B-Z increases, and a decrease in one case, on a timescale of seconds, accompanied by large electric fields with amplitudes > several tens of mV/m. Spatial scale lengths were of the order of the ion inertial length and the ion gyroradius. The inertial term in the momentum equation and the Hall term in the generalized Ohm's law were sometimes non-negligible. These small-scale variations are discussed in terms of the ballooning/interchange instability and kinetic Alfven waves among others. It is inferred that physics of multiple scales was involved in the dynamics of this dipolarization event.
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| 12. |
- Matsui, H., et al.
(författare)
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Dipolarization in the inner magnetosphere during a geomagnetic storm on 7 October 2015
- 2016
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 43:18, s. 9397-9405
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Tidskriftsartikel (refereegranskat)abstract
- A dipolarization event was observed by the Magnetospheric Multiscale (MMS) spacecraft at L = 3.8 and 19.8 magnetic local time starting at similar to 23:42:36 UT on 7 October 2015. The magnetic and electric fields showed initially coherent variations between the spacecraft. The sunward convection turned tailward after the dipolarization. The observation is interpreted in terms of the pressure balance or the momentum equation. This was followed by a region traversed where the fields were irregular. The scale length was of the order of the ion gyroradius, suggesting the kinetic nature of the fluctuations. Combination of the multi-instrument, multispacecraft data reveals a more detailed picture of the dipolarization event in the inner magnetosphere. Conjunction ionosphere-plasmasphere observations from DMSP, two-dimensional GPS total electron content, the Millstone Hill midlatitude incoherent scatter radar, and AMPERE measurements imply that MMS observations are located on the poleward edge of the ionospheric trough where Region 2 field-aligned currents flow.
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| 13. |
- Matsui, H., et al.
(författare)
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Relativistic Electron Increase During Chorus Wave Activities on the 6-8 March 2016 Geomagnetic Storm
- 2017
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 122:11, s. 11302-11319
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Tidskriftsartikel (refereegranskat)abstract
- There was a geomagnetic storm on 6-8 March 2016, in which Van Allen Probes A and B separated by similar to 2.5 h measured increase of relativistic electrons with energies approximately several hundred keV to 1 MeV. Simultaneously, chorus waves were measured by both Van Allen Probes and Magnetospheric Multiscale (MMS) mission. Some of the chorus elements were rising tones, possibly due to nonlinear effects. These measurements are compared with a nonlinear theory of chorus waves incorporating the inhomogeneity ratio and the field equation. From this theory, a chorus wave profile in time and one-dimensional space is simulated. Test particle calculations are then performed in order to examine the energization rate of electrons. Some electrons are accelerated, although more electrons are decelerated. The measured time scale of the electron increase is inferred to be consistent with this nonlinear theory.
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| 14. |
- Wimmer, K., et al.
(författare)
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First spectroscopy of Ti-61 and the transition to the Island of Inversion at N=40
- 2019
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Ingår i: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 792, s. 16-20
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Tidskriftsartikel (refereegranskat)abstract
- Isomeric states in Ti-59,Ti-61 have been populated in the projectile fragmentation of a 345 AMeV( 238)U beam at the Radioactive Isotope Beam Factory. The decay lifetimes and delayed gamma-ray transitions were measured with the EURICA array. Besides the known isomeric state in Ti-59, two isomeric states in Ti-61 are observed for the first time. Based on the measured lifetimes, transition multipolarities as well as tentative spins and parities are assigned. Large-scale shell model calculations based on the modified LNPS interaction show that both Ti-59 and Ti-61 belong to the Island of Inversion at N = 40 with ground state configurations dominated by particle-hole excitations to the g(9/2 )and d(5/2) orbits.
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| 15. |
- Wimmer, K., et al.
(författare)
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Isomeric states in neutron-rich nuclei near N=40
- 2021
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Ingår i: Physical Review C. - : American Physical Society (APS). - 2469-9985 .- 2469-9993. ; 104:1
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Tidskriftsartikel (refereegranskat)abstract
- Neutron-rich nuclei in the vicinity of the N = 40 island of inversion are characterized by shell evolution and exhibit deformed ground states. In several nuclei isomeric states have been observed and attributed to excitations to the intruder neutron 1g(9/2) orbital. In the present paper we searched for isomeric states in nuclei around N = 40, Z = 22 produced by projectile fragmentation at the Radioactive Isotope Beam Factory. Delayed. rays were detected by the Euroball RIKEN Cluster Array germanium detector array gamma High statistics data allowed for an updated decay scheme of V-60. The lifetime of an isomeric state in V-64 was measured for the first time in the present experiment. A previously unobserved isomeric state was discovered in Sc-58. The measured lifetime suggests a parity changing transition, originating from an odd number of neutrons in the 1g(9/2) orbital. The nature of the isomeric state in Sc-58 is, thus, different from isomers in the less exotic V and Sc nuclei.
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| 16. |
- Ackloo, S, et al.
(författare)
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Target 2035 - an update on private sector contributions
- 2023
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Ingår i: RSC medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 14:6, s. 1002-1011
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Target 2035, an international federation of biomedical scientists from the public and private sectors, is leveraging ‘open’ principles to develop a pharmacological tool for every human protein.
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| 17. |
- Caputi, K. I., et al.
(författare)
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ALMA Lensing Cluster Survey: An ALMA Galaxy Signposting a MUSE Galaxy Group at z=4.3 Behind "El Gordo"
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 908:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a Multi Unit Spectroscopic Explorer (MUSE) galaxy group at z = 4.32 lensed by the massive galaxy cluster ACT-CL J0102-4915 (aka El Gordo) at z = 0.87, associated with a 1.2 mm source that is at a 2.07 0.88 kpc projected distance from one of the group galaxies. Three images of the whole system appear in the image plane. The 1.2 mm source has been detected within the Atacama Large Millimetre/submillimetre Array (ALMA) Lensing Cluster Survey (ALCS). As this ALMA source is undetected at wavelengths lambda < 2 mu m, its redshift cannot be independently determined, however, the three lensing components indicate that it belongs to the same galaxy group at z = 4.32. The four members of the MUSE galaxy group have low to intermediate stellar masses (similar to 10(7)-10(10) M) and star formation rates (SFRs) of 0.4-24 M yr(-1), resulting in high specific SFRs (sSFRs) for two of them, which suggest that these galaxies are growing fast (with stellar mass doubling times of only similar to 2 x 10(7) yr). This high incidence of starburst galaxies is likely a consequence of interactions within the galaxy group, which is compact and has high velocity dispersion. Based on the magnification-corrected sub-/millimeter continuum flux density and estimated stellar mass, we infer that the ALMA source is classified as an ordinary ultra-luminous infrared galaxy (with associated dust-obscured SFR similar to 200-300 M yr(-1)) and lies on the star formation main sequence. This reported case of an ALMA/MUSE group association suggests that some presumably isolated ALMA sources are in fact signposts of richer star-forming environments at high redshifts.
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| 18. |
- Farrugia, C. J., et al.
(författare)
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MMS Observations of Reconnection at Dayside Magnetopause Crossings During Transitions of the Solar Wind to Sub-Alfvénic Flow
- 2017
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing Ltd. - 2169-9380 .- 2169-9402. ; 122:10, s. 9934-9951
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Tidskriftsartikel (refereegranskat)abstract
- We present MMS observations during two dayside magnetopause crossings under hitherto unexamined conditions: (i) when the bow shock is weakening and the solar wind transitioning to sub-Alfvénic flow and (ii) when it is reforming. Interplanetary conditions consist of a magnetic cloud with (i) a strong B (∼20 nT) pointing south and (ii) a density profile with episodic decreases to values of ∼0.3 cm−3 followed by moderate recovery. During the crossings the magnetosheath magnetic field is stronger than the magnetosphere field by a factor of ∼2.2. As a result, during the outbound crossing through the ion diffusion region, MMS observed an inversion of the relative positions of the X and stagnation (S) lines from that typically the case: the S line was closer to the magnetosheath side. The S line appears in the form of a slow expansion fan near which most of the energy dissipation is taking place. While in the magnetosphere between the crossings, MMS observed strong field and flow perturbations, which we argue to be due to kinetic Alfvén waves. During the reconnection interval, whistler mode waves generated by an electron temperature anisotropy (Te⊥>Te∥) were observed. Another aim of the paper is to distinguish bow shock-induced field and flow perturbations from reconnection-related signatures. The high-resolution MMS data together with 2-D hybrid simulations of bow shock dynamics helped us to distinguish between the two sources. We show examples of bow shock-related effects (such as heating) and reconnection effects such as accelerated flows satisfying the Walén relation.
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| 19. |
- Matsui, H., et al.
(författare)
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Revision of empirical electric field modeling in the inner magnetosphere using Cluster data
- 2013
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Ingår i: Journal of Geophysical Research-Space Physics. - : American Geophysical Union (AGU). - 2169-9380. ; 118:7, s. 4119-4134
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Tidskriftsartikel (refereegranskat)abstract
- Using Cluster data from the Electron Drift (EDI) and the Electric Field and Wave (EFW) instruments, we revise our empirically-based, inner-magnetospheric electric field (UNH-IMEF) model at 22.662 mV/m; K-p<1, 1K(p)<2, 2K(p)<3, 3K(p)<4, 4K(p)<5, and K(p)4(+). Patterns consist of one set of data and processing for smaller activities, and another for higher activities. As activity increases, the skewed potential contour related to the partial ring current appears on the nightside. With the revised analysis, we find that the skewed potential contours get clearer and potential contours get denser on the nightside and morningside. Since the fluctuating components are not negligible, standard deviations from the modeled values are included in the model. In this study, we perform validation of the derived model more extensively. We find experimentally that the skewed contours are located close to the last closed equipotential, consistent with previous theories. This gives physical context to our model and serves as one validation effort. As another validation effort, the derived results are compared with other models/measurements. From these comparisons, we conclude that our model has some clear advantages over the others.
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| 20. |
- Muller, S, et al.
(författare)
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Target 2035 - update on the quest for a probe for every protein
- 2022
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Ingår i: RSC medicinal chemistry. - : Royal Society of Chemistry (RSC). - 2632-8682. ; 13:1, s. 13-21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Twenty years after the publication of the first draft of the human genome, our knowledge of the human proteome is still fragmented. Target 2035 aims to develop a pharmacological modulator for every protein in the human proteome to fill this gap.
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| 21. |
- Pasquini, L., et al.
(författare)
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Z-scores of the fetal aortic isthmus and duct: an aid to assessing arch hypoplasia
- 2007
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Ingår i: Ultrasound Obstet Gynecol. - 0960-7692. ; 29:6, s. 628-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Prenatal diagnosis of isolated coarctation of the aorta suffers from high false positive and false negative rates. The aim of our study was to develop Z-scores for the aortic isthmus in normal fetuses as a reference for fetuses with suspected coarctation. METHODS: The aortic isthmal diameter, immediately proximal to the insertion of the arterial duct, was measured prospectively in the transverse (three vessel and trachea) and sagittal views in 221 normal fetuses at 18 to 37 weeks' gestation. The ductal diameter was measured immediately before it entered the descending aorta in the same view. All measurements were repeated three times by a single investigator and averaged. A second investigator re-measured the images of 50 cases to assess interobserver variability. Z-scores were created relating isthmal and ductal diameters to femur length and gestational age. The ratio between the isthmal and ductal diameters was calculated. RESULTS: The formula used to calculate Z-scores for the three diameters was: [ln(measured isthmal diameter) - (m ln(femur length or gestational age) + c)]/root MSE, where c is the intercept, m is a multiplier and MSE is the mean squared error. The ratio between isthmal and ductal diameters was close to a constant value of 1 (95% CI 0.97-1.01), regardless of the value of femur length or gestational age. CONCLUSION: We have defined Z-scores for the fetal aortic isthmus and arterial duct measured in the three vessels and trachea view and for the isthmus in the sagittal plane. In suspected coarctation, these Z-scores and the isthmal to ductal ratio may help in longitudinal assessment of the aortic arch and aid in the prenatal diagnosis of coarctation.
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| 22. |
- Recchia, F., et al.
(författare)
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Isomer spectroscopy in odd–even Ti isotopes : Approaching n = 40
- 2019
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Ingår i: Acta Physica Polonica B. - : Jagellonian University. - 0587-4254 .- 1509-5770. ; 50:3, s. 669-674
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of the evolution of the shell structure in nuclei far from stability is based on the study of some key nuclei. Nuclei at or next to double shell closures play a special role in this. Presently, a lot of discussion is concentrated on the neutron-rich calcium isotopes, which provide a rich testing ground for various nuclear models with several traditional and new magic numbers. 60 Ca is now almost within reach with the most advanced radioactive beam facilities. In order to investigate the evolution of the shell gap at N = 40, the configuration of states in the odd–even titanium isotopes up to N = 37 ( 59 Ti) have been studied. In order to experimentally access the shell gap at N = 40, it is nowadays within the reach of the most advanced facility the investigation of neutron hole configuration states in odd–even titanium isotopes up to N = 37, in the 59 Ti nucleus. Such states correspond to relatively simple configurations that constitute a challenging testing ground for effective nuclear interactions. The new data obtained in our experiment allows to place the present predictions concerning the shell closure at N = 40 in the calcium region on a more solid ground.
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| 23. |
- Skoglund, Lena, et al.
(författare)
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Novel Progranulin Mutation Detected in 2 Patients With FTLD
- 2011
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Ingår i: Alzheimer Disease and Associated Disorders. - : Lippincott Williams & Wilkins. - 0893-0341 .- 1546-4156. ; 25:2, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions, and linkage to chromosome 17 was recently found to be caused by mutations in the progranulin (PGRN) gene. In this study, we screened a group of 51 FTLD patients for PGRN mutations and identified a novel exon 6 splice donor site deletion (IVS6+5_8delGTGA) in 2 unrelated patients. This mutation displayed an altered splicing pattern generating 2 aberrant transcripts and causing frameshifts of the coding sequence, premature termination codons, and a near absence of PGRN mRNA from the mutated alleles most likely through nonsense-mediated decay. The subsequent PGRN haploinsufficiency is consistent with previously described PGRN mutations. We present a molecular characterization of the IVS6+5_8delGTGA mutation and also describe clinical and neuropathologic features from the 2 patients carrying this PGRN mutation. From the screening of these 51 FTLD patients, we could also identify the earlier reported mutation Gln130fs, and several coding sequence variants that are most likely nonpathogenic.
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| 24. |
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| 25. |
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| 26. |
- Erickson, P. J., et al.
(författare)
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Multipoint MMS observations of fine-scale SAPS structure in the inner magnetosphere
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:14, s. 7294-7300
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Tidskriftsartikel (refereegranskat)abstract
- We present detailed observations of dynamic, fine-scale inner magnetosphere-ionosphere coupling at approximate to 3.9R(E) in the Region 2 Birkeland field-aligned current (FAC). We find that observed electrodynamic spatial/temporal scales are primarily characteristic of magnetically mapped ionospheric structure. On 15 September 2015, conjugate Magnetospheric Multiscale (MMS) spacecraft and Millstone Hill radar observations show plasmasphere boundary region subauroral polarization stream (SAPS) electric fields at L = 4.0-4.2 near 21 MLT. MMS observations reveal high-altitude approximate to 1mV/m fine-scale radial and azimuthal electric field perturbations over 0.15L with high spatial coherence over 2-3min and show outward motion within a broader FAC of approximate to 0.12A/m(2). Our analysis shows that MMS electric field fluctuations are most likely reflective of SAPS ionospheric structure at scales of approximate to 22km and with ionospheric closure of small-scale filamentary FAC perturbations. The results highlight the ionosphere's importance in regulating fine-scale magnetosphere-ionosphere structure.
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| 27. |
- Farrugia, C. J., et al.
(författare)
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Effects in the Near-Magnetopause Magnetosheath Elicited by Large-Amplitube Alfvenic Fluctuations Terminating in a Field and Flow Discontinuity
- 2018
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 123:11, s. 8983-9004
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report on a sequence of large-amplitude Alfvenic fluctuations terminating in a field and flow discontinuity and their effects on electromagnetic fields and plasmas in the near-magnetopause magnetosheath. An arc-polarized structure in the magnetic field was observed by the Time History of Events and Macroscale Interactions during Substorms-C in the solar wind, indicative of nonlinear Alfven waves. It ends with a combined tangential discontinuity/vortex sheet, which is strongly inclined to the ecliptic plane and at which there is a sharp rise in the density and a drop in temperature. Several effects resulting from this structure were observed by the Magnetospheric Multiscale spacecraft in the magnetosheath close to the subsolar point (11:30 magnetic local time) and somewhat south of the geomagnetic equator (-33 degrees magnetic latitude): (i) kinetic Alfven waves; (ii) a peaking of the electric and magnetic field strengths where E . J becomes strong and negative (-1 nW/m(3)) just prior to an abrupt dropout of the fields; (iii) evolution in the pitch angle distribution of energetic (a few tens of kilo-electron-volts) ions (H+, Hen+, and On+) and electrons inside a high-density region, which we attribute to gyrosounding of the tangential discontinuity/vortex sheet structure passing by the spacecraft; (iv) field-aligned acceleration of ions and electrons that could be associated with localized magnetosheath reconnection inside the high-density region; and (v) variable and strong flow changes, which we argue to be unrelated to reconnection at partial magnetopause crossings and likely result from deflections of magnetosheath flow by a locally deformed, oscillating magnetopause.
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| 28. |
- Farrugia, C. J., et al.
(författare)
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Magnetospheric Multiscale Mission observations and non-force free modeling of a flux transfer event immersed in a super-Alfvenic flow
- 2016
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 43:12, s. 6070-6077
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Tidskriftsartikel (refereegranskat)abstract
- We analyze plasma, magnetic field, and electric field data for a flux transfer event (FTE) to highlight improvements in our understanding of these transient reconnection signatures resulting from high-resolution data. The similar to 20 s long, reverse FTE, which occurred south of the geomagnetic equator near dusk, was immersed in super-Alfvenic flow. The field line twist is illustrated by the behavior of flows parallel/perpendicular to the magnetic field. Four-spacecraft timing and energetic particle pitch angle anisotropies indicate a flux rope (FR) connected to the Northern Hemisphere and moving southeast. The flow forces evidently overcame the magnetic tension. The high-speed flows inside the FR were different from those outside. The external flows were perpendicular to the field as expected for draping of the external field around the FR. Modeling the FR analytically, we adopt a non-force free approach since the current perpendicular to the field is nonzero. It reproduces many features of the observations.
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| 29. |
- Gentil, Emmanuel C., et al.
(författare)
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Models for waste life cycle assessment : Review of technical assumptions
- 2010
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Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 30:12, s. 2636-2648
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Forskningsöversikt (refereegranskat)abstract
- A number of waste life cycle assessment (LCA) models have been gradually developed since the early 1990s, in a number of countries, usually independently from each other. Large discrepancies in results have been observed among different waste LCA models, although it has also been shown that results from different LCA studies can be consistent. This paper is an attempt to identify, review and analyse methodologies and technical assumptions used in various parts of selected waste LCA models. Several criteria were identified, which could have significant impacts on the results, such as the functional unit, system boundaries, waste composition and energy modelling. The modelling assumptions of waste management processes, ranging from collection, transportation, intermediate facilities, recycling, thermal treatment, biological treatment, and landfilling, are obviously critical when comparing waste LCA models. This review infers that some of the differences in waste LCA models are inherent to the time they were developed. It is expected that models developed later, benefit from past modelling assumptions and knowledge and issues. Models developed in different countries furthermore rely on geographic specificities that have an impact on the results of waste LCA models. The review concludes that more effort should be employed to harmonise and validate non-geographic assumptions to strengthen waste LCA modelling.
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| 30. |
- Ingelsson, Martin, et al.
(författare)
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No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer's disease brain
- 2006
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 112:4, s. 439-449
-
Tidskriftsartikel (refereegranskat)abstract
- Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R tau) and without (3R tau) exon 10, is believed to be a pathological consequence of certain tau mutations causing frontotemporal dementia. By assessing protein and mRNA levels of 4R tau and 3R tau in 27 AD and 20 control temporal cortex, we investigated whether altered tau splicing is a feature also in Alzheimer's disease (AD). However, apart from an expected increase of sarcosyl-insoluble tau in AD, there were no significant differences between the groups. Next, by laser-capture microscopy and quantitative PCR, we separately analyzed CA1 hippocampal neurons with and without neurofibrillary pathology from six of the AD and seven of the control brains. No statistically significant differences in 4R tau/3R tau mRNA were found between the different subgroups. Moreover, we confirmed the absence of significant ratio differences in a second data set with laser-captured entorhinal cortex neurons from four AD and four control brains. Finally, the 4R tau/3R tau ratio in CA1 neurons was roughly half of the ratio in temporal cortex, indicating region-specific differences in tau mRNA splicing. In conclusion, this study indicated region-specific and possibly cell-type-specific tau splicing but did not lend any support to overt changes in alternative splicing of tau exon 10 being an underlying factor in AD pathogenesis.
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| 31. |
- Leclere, David, et al.
(författare)
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Bending the curve of terrestrial biodiversity needs an integrated strategy
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 585:7826, s. 551-556
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Tidskriftsartikel (refereegranskat)abstract
- Increased efforts are required to prevent further losses to terrestrial biodiversity and the ecosystem services that it provides(1,2). Ambitious targets have been proposed, such as reversing the declining trends in biodiversity(3); however, just feeding the growing human population will make this a challenge(4). Here we use an ensemble of land-use and biodiversity models to assess whether-and how-humanity can reverse the declines in terrestrial biodiversity caused by habitat conversion, which is a major threat to biodiversity(5). We show that immediate efforts, consistent with the broader sustainability agenda but of unprecedented ambition and coordination, could enable the provision of food for the growing human population while reversing the global terrestrial biodiversity trends caused by habitat conversion. If we decide to increase the extent of land under conservation management, restore degraded land and generalize landscape-level conservation planning, biodiversity trends from habitat conversion could become positive by the mid-twenty-first century on average across models (confidence interval, 2042-2061), but this was not the case for all models. Food prices could increase and, on average across models, almost half (confidence interval, 34-50%) of the future biodiversity losses could not be avoided. However, additionally tackling the drivers of land-use change could avoid conflict with affordable food provision and reduces the environmental effects of the food-provision system. Through further sustainable intensification and trade, reduced food waste and more plant-based human diets, more than two thirds of future biodiversity losses are avoided and the biodiversity trends from habitat conversion are reversed by 2050 for almost all of the models. Although limiting further loss will remain challenging in several biodiversity-rich regions, and other threats-such as climate change-must be addressed to truly reverse the declines in biodiversity, our results show that ambitious conservation efforts and food system transformation are central to an effective post-2020 biodiversity strategy. To promote the recovery of the currently declining global trends in terrestrial biodiversity, increases in both the extent of land under conservation management and the sustainability of the global food system from farm to fork are required.
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| 32. |
- Matsui, H., et al.
(författare)
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Characteristics of storm time electric fields in the inner magnetosphere derived from Cluster data
- 2010
-
Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115, s. A11215-
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Tidskriftsartikel (refereegranskat)abstract
- Storm-time electric fields in the inner magnetosphere measured by Cluster are reported in this study. First, we show two events around the time when Dst index is at a minimum. The electric field possibly related to subauroral ion drifts and/or undershielding is measured inside the inner edge of the electron plasma sheet in the eveningside. For the second event observed in the nightside, the electric field is partly related to dipolarization and is considered as inductive. An electric field without coincident magnetic signatures is also observed. Spatial coherence of the electric field is not large when we check multispacecraft data. It is inferred that the electric field in the magnetotail penetrates inside the region 1 current, while it is not clear about the electric field within the region 2 current from our data. Then superposed epoch analyses using 71 storms are performed. Electric fields at R = 3.5-6R(E) and less than 25 degrees of magnetic latitudes are enhanced around the minimum Dst at all magnetic local times. Electric fields during the recovery phase decay on a time scale shorter than that of Dst index, which could be interpreted in terms of the relation between electric field and ring current during that storm phase. AC electric fields are generally larger than DC electric fields, indicating that the former component might play some role in accelerating ring current particles. These results will be useful to update our empirical electric field model.
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| 33. |
- Matsui, H., et al.
(författare)
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Derivation of inner magnetospheric electric field (UNH-IMEF) model using Cluster data set
- 2008
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 26:9, s. 2887-2898
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Tidskriftsartikel (refereegranskat)abstract
- We derive an inner magnetospheric electric field (UNH-IMEF) model at L=2-10 using primarily Cluster electric field data for more than 5 years between February 2001 and October 2006. This electric field data set is divided into several ranges of the interplanetary electric field (IEF) values measured by ACE. As ring current simulations which require electric field as an input parameter are often performed at L=2-6.6, we have included statistical results from ground radars and low altitude satellites inside the perigee of Cluster in our data set (L similar to 4). Electric potential patterns are derived from the average electric fields by solving an inverse problem. The electric potential pattern for small IEF values is probably affected by the ionospheric dynamo. The magnitudes of the electric field increase around the evening local time as IEF increases, presumably due to the sub-auroral polarization stream (SAPS). Another region with enhanced electric fields during large IEF periods is located around 9 MLT at L>8, which is possibly related to solar wind-magnetosphere coupling. Our potential patterns are consistent with those derived from self-consistent simulations. As the potential patterns can be interpolated/extrapolated to any discrete IEF value within measured ranges, we thus derive an empirical electric potential model. The performance of the model is evaluated by comparing the electric field derived from the model with original one measured by Cluster and mapped to the equator. The model is open to the public through our website.
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| 34. |
- Matsui, H., et al.
(författare)
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Multi-spacecraft observations of small-scale fluctuations in density and fields in plasmaspheric plumes
- 2012
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 30:3, s. 623-637
-
Tidskriftsartikel (refereegranskat)abstract
- In this event study, small-scale fluctuations in plasmaspheric plumes with time scales of similar to 10 s to minutes in the spacecraft frame are examined. In one event, plasmaspheric plumes are observed by Cluster, while IMAGE measured density enhancement at a similar location. Fluctuations in density exist in plumes as detected by Cluster and are accompanied by fluctuations in magnetic fields and electric fields. Magnetic fluctuations are transverse and along the direction of the plumes. The E/B ratio is smaller than the Alfv,n velocity. Another similar event is briefly presented. We then consider physical properties of the fluctuations. Alfv,n mode modulated by the feedback instability is one possibility, although non-local generation is likely. It is hard to show that the fluctuations represent a fast mode. Interchange motion is possible due to the consistency between measurements and expectations. The energy source could be a pressure or density gradient in plasmaspheric plumes. When more events are accumulated so that statistical analysis becomes feasible, this type of study will be useful to understand the time evolution of plumes.
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| 35. |
- Matsui, S, et al.
(författare)
-
Beneficial effect of angiotensin-converting enzyme inhibitor on dilated cardiomyopathy induced by autoimmune mechanism against beta1-adrenoceptor.
- 2000
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Ingår i: Journal of cardiovascular pharmacology. - 0160-2446. ; 36 Suppl 2
-
Tidskriftsartikel (refereegranskat)abstract
- We have shown that a peptide corresponding to the sequence of the second extracellular loop of the human beta1-adrenoceptor (beta1-peptide) was able to induce an autoimmune cardiomyopathy in rabbits. In this study, we examined the effect of angiotensin-converting enzyme inhibitor (ACEI) on beta1-peptide-induced cardiomyopathy. Rabbits were divided into four groups: (1) control group (n= 6) receiving saline injection; (2) beta1-peptide group (n = 8) immunized with beta1-peptide; (3) ACEI group (n = 6), lisinopril (3 mg/day) given orally and receiving saline injection; and (4) ACEI + beta1-peptide group (n = 7), lisinopril (3 mg/day) given orally and immunized with beta1-peptide. Our results showed that, after 1 year, all rabbits in the beta1-peptide group had an increase in heart weight, wall thinning and dilatations of both ventricles as compared with rabbits in the ACEI + beta1-peptide group that had normal heart weight and shape. All rabbits in the beta1-peptide group exhibited multifocal degeneration and necrosis of myocardial cells with moderate infiltration of inflammatory cells. In the ACEI + beta1-peptide group, three rabbits showed focal degeneration and necrosis of myocardial cells accompanied by mononuclear cells. The lesions in this group were apparently less marked than those in the beta1-peptide group. In conclusion, ACEI protects the myocardium from injury induced by an autoimmune mechanism against beta1-adrenoceptor.
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| 36. |
- Matsui, S, et al.
(författare)
-
Protective effect of bisoprolol on beta-1 adrenoceptor peptide-induced autoimmune myocardial damage in rabbits.
- 2000
-
Ingår i: Herz. - 0340-9937. ; 25:3, s. 267-70
-
Tidskriftsartikel (refereegranskat)abstract
- Idiopathic dilated cardiomyopathy is a severe disease of unknown etiology. Accumulating evidence suggests that agonist-like autoantibodies against the beta 1 adrenoceptor in the circulation of dilated cardiomyopathy may play an important role. The aim of this study was to evaluate the effects of the selective beta 1-adrenoceptor blocker, bisoprolol, on beta 1-adrenoceptor peptide induced autoimmune myocardial damage. In the animal model of autoimmune cardiomyopathy induced by active immunization of rabbits with beta 1-adrenoceptor peptide, bisoprolol was given at a dose of 3 mg/day throughout the study period. Our results showed high titer of anti-beta 1-adrenoceptor antibody in the immunized group throughout the study but not in the group receiving only bisoprolol. Cross-reactivity to beta 2 adrenoceptors was observed in some of the immunized rabbits, but disappeared almost entirely after 6 months. As compared to the beta 1-adrenoceptor peptide immunized group without bisoprolol treatment, bisoprolol treated beta 1-receptor peptide immunized group showed increase in the wall thickness and decreases in cavity dimension in anatomical measurements and only mild alterations in macro- and microscopic examinations. Thus, our study clearly demonstrated a beneficial effect of bisoprolol in rabbits who have developed autoimmune myocardial damage.
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| 37. |
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| 38. |
- Michels, F., et al.
(författare)
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Searching for consensus in the approach to patients with chronic lateral ankle instability: ask the expert
- 2018
-
Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:7, s. 2095-2102
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to propose recommendations for the treatment of patients with chronic lateral ankle instability (CAI) based on expert opinions. A questionnaire was sent to 32 orthopaedic surgeons with clinical and scientific experience in the treatment of CAI. The questions were related to preoperative imaging, indications and timing of surgery, technical choices, and the influence of patient-related aspects. Thirty of the 32 invited surgeons (94%) responded. Consensus was found on several aspects of treatment. Preoperative MRI was routinely recommended. Surgery was considered in patients with functional ankle instability after 3-6 months of non-surgical treatment. Ligament repair is still the treatment of choice in patients with mechanical instability; however, in patients with generalized laxity or poor ligament quality, lateral ligament reconstruction (with grafting) of both the ATFL and CFL should be considered. Most surgeons request an MRI during the preoperative planning. There is a trend towards earlier surgical treatment (after failure of non-surgical treatment) in patients with mechanical ligament laxity (compared with functional instability) and in high-level athletes. This study proposes an assessment and a treatment algorithm that may be used as a recommendation in the treatment of patients with CAI.
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| 39. |
- Miura, R.E., et al.
(författare)
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A giant molecular cloud catalogue in the molecular disc of the elliptical galaxy NGC 5128 (Centaurus A)
- 2021
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 504:4, s. 6198-6215
-
Tidskriftsartikel (refereegranskat)abstract
- We present the first census of giant molecular clouds (GMCs) complete down to 106 M⊙ and within the inner 4 kpc of the nearest giant elliptical and powerful radio galaxy, Centaurus A. We identified 689 GMCs using CO(1-0) data with 1 arcsec spatial resolution (∼20 pc) and 2 km s-1 velocity resolution obtained with the Atacama Large Millimeter/submillimeter Array. The I(CO)-N(H2) conversion factor based on the virial method is XCO = (2 ± 1) × 1020 cm-2(K km s-1)-1 for the entire molecular disc, consistent with that of the discs of spiral galaxies including the Milky Way, and XCO = (5 ± 2) × 1020 cm-2(K km s-1)-1 for the circumnuclear disc (CND; within a galactocentric radius of 200 pc). We obtained the GMC mass spectrum distribution and find that the best truncated power-law fit for the whole molecular disc, with index γ≃ -2.41 ± 0.02 and upper cut-off mass $\sim \! 1.3\times 10^{7}\, \mathrm{M}_{\odot }$, is also in agreement with that of nearby disc galaxies. A trend is found in the mass spectrum index from steep to shallow as we move to inner radii. Although the GMCs are in an elliptical galaxy, the general GMC properties in the molecular disc are as in spiral galaxies. However, in the CND, large offsets in the line-width-size scaling relations (∼0.3 dex higher than those in the GMCs in the molecular disc), a different XCO factor, and the shallowest GMC mass distribution shape (γ= -1.1 ± 0.2) all suggest that there the GMCs are most strongly affected by the presence of the active galactic nucleus and/or shear motions.
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| 40. |
- Ozolins, Oskars, et al.
(författare)
-
Error-Free 108 Gbps On-Off Keying Link for Optical Interconnect Applications
- 2022
-
Ingår i: 2022 European Conference on Optical Communication, ECOC 2022. - : Institute of Electrical and Electronics Engineers Inc.. - 9781957171159
-
Konferensbidrag (refereegranskat)abstract
- We demonstrate an error-free 108 Gbps OOK link using a C-band externally modulated laser with 3.3 dBm of modulated output power and an O-band directly modulated laser with 7.3 dBm of modulated output power. This paves the way forward for high-speed optical interconnects without FEC.
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| 41. |
- Pang, Xiaodan, Dr., et al.
(författare)
-
200 Gb/s Unamplified IM/DD Transmission over 20-km SMF with an O-band Low-Chirp Directly Modulated Laser
- 2022
-
Ingår i: 2022 European Conference on Optical Communication, ECOC 2022. - : Institute of Electrical and Electronics Engineers Inc.. - 9781957171159
-
Konferensbidrag (refereegranskat)abstract
- 200 Gb/s IM/DD transmission over 20-km SMF is demonstrated without any optical amplifiers, achieving BER below the 6.25%-overhead HD-FEC limit, enabled by a broadband and high-power DML with low-complexity digital equalizations.
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| 42. |
- Proletov, Ian, et al.
(författare)
-
Primary and secondary glomerulonephritides 1.
- 2014
-
Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
-
Tidskriftsartikel (refereegranskat)
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| 43. |
- Puhl-Quinn, P. A., et al.
(författare)
-
An effort to derive an empirically based, inner-magnetospheric electric field model : Merging Cluster EDI and EFW data
- 2008
-
Ingår i: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 70:2-4, s. 564-573
-
Tidskriftsartikel (refereegranskat)abstract
- A key ingredient for modelling many inner-magnetospheric processes is the realistic representation of the spatio-temporal dynamics of the inner-magnetospheric electric field, or, IMEF The Cluster Mission provides a unique opportunity to construct an IMEF model using electric field measurements from both the electron drift instrument (EDI) and the electric fields and waves instrument (EFW). A superset of IMEF data is formed by merging EDI and EFW data. Challenges presented by the merging process include the handling of compromised perpendicular electric field (E-L) calculations, electric field offsets, scaling problems, and spurious fields. The present goal is to produce the highest quality merged IMEF data set possible which is minimally affected by these issues. Preliminary investigation of the merging process on Cluster I for the years 2001-2003 has revealed that merging is a worthwhile exercise. The data sets are shown to be complementary, and the IMEF merged data set is superior to either data set alone in terms of improved spatial coverage, and coverage of a wider range of geomagnetic activity levels. Preliminary use of the merged IMEF data set to construct a parameterized, equatorial, electric field model for the inner magnetosphere, the UNH-IMEF model, is also presented. The electric field morphology produced by this preliminary version of the UNH-IMEF model shows the expected sensitivity to IMF orientation.
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| 44. |
- Puhl-Quinn, P. A., et al.
(författare)
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Cluster and DMSP observations of SAID electric fields
- 2007
-
Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 112:A5, s. A05219-
-
Tidskriftsartikel (refereegranskat)abstract
- [1] We report on magnetically conjugate Cluster and the Defense Meteorological Satellite Program (DMSP) satellite observations of subauroral ion drifts (SAID) during moderate geomagnetic activity levels on 8 April 2004. To our knowledge, the field-aligned separation of DMSP and Cluster (approximate to 28,000 km) is the largest separation ever analyzed with respect to the SAID phenomenon. Nonetheless, we show coherent, subauroral magnetosphere-ionosphere (MI) coupling along an entire field line in the post-dusk sector. The four Cluster satellites crossed SAID electric field channels with meridional magnitude E-M of 25 mV/m in situ and latitudinal extent Delta Lambda approximate to 0.5 degrees in the southern and northern hemispheres near 07:00 and 07:30 UT, respectively. Cluster was near perigee (R approximate to 4 R-E) and within 5 degrees (15 degrees) of the magnetic equator for the southern ( northern) crossing. The SAID were located near the plasmapause-within the ring current-plasmasphere overlap region. Downward field-aligned current signatures were observed across both SAID crossings. The most magnetically and temporally conjugate SAID field from DMSP F16A at 07:12 UT was practically identical in latitudinal size to that mapped from Cluster. Since the DMSP ion drift meter saturated at 3000 m/s (or similar to 114 mV/m) and the electrostatically mapped value for E-M from Cluster exceeded 300 mV/m, a magnitude comparison of E-M was not possible. Although the conjugate measurements show similar large-scale SAID features, the differences in substructure highlight the physical and chemical diversity of the conjugate regions.
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| 45. |
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| 46. |
- Wallukat, G, et al.
(författare)
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Autoantibodies against M2 muscarinic receptors in patients with cardiomyopathy display non-desensitized agonist-like effects.
- 1999
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Ingår i: Life sciences. - 0024-3205. ; 64:6-7, s. 465-9
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Tidskriftsartikel (refereegranskat)abstract
- Circulating autoantibodies against the human M2 muscarinic receptors have been previously shown in 38% of patients with idiopathic dilated cardiomyopathy. The functional properties of these autoantibodies are reported herein. They were able to decrease the cell beating frequency of myocytes in cultured neonatal rat heart cells in a dose-dependent manner without desensitization over a period of more than 5 hours whereas the non-specific muscarinic receptor agonist carbachol also inhibited the heart cell beating frequency but was desensitized within 1 hour. In the same cell culture, anti-M2 muscarinic receptor autoantibodies were not able to induce internalization of muscarinic receptor whereas carbachol did. These results demonstrate for the first time that anti-M2 muscarinic receptor autoantibodies from patients with idiopathic dilated cardiomyopathy have stimulatory muscarinic activity in vitro, which differ from normal muscarinic agonists by non-desensitization.
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