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- McLinden, C. A., et al.
(författare)
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OSIRIS: A Decade of Scattered Light
- 2012
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Ingår i: Bulletin of the American Meteorological Society. - 0003-0007 .- 1520-0477. ; 93:12, s. 1845-1863
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Tidskriftsartikel (refereegranskat)abstract
- Into year 11 of a 2-yr mission, OSIRIS is redefining how limb-scattered sunlight can be used to probe the atmosphere, even into the upper troposphere.
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- Haley, C. S., et al.
(författare)
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Retrievals of stratospheric O3 and NO2 profiles from Odin Optical Spectrograph and InfraRed Imager System (OSIRIS) limb-scattered sunlight measurements
- 2004
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 109:D16
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Tidskriftsartikel (refereegranskat)abstract
- Scientific studies of the major environmental questions of global warming and ozone depletion require global data sets of atmospheric constituents with relevant temporal and spatial resolution. In this paper global number density profiles of O3 and NO2 are retrieved from Odin/OSIRIS limb-scattered sunlight measurements, using the Maximum A Posteriori estimator. Differential Optical Absorption Spectroscopy is applied to OSIRIS radiances as an intermediate step, using the wavelength windows 571-617 nm for O3 and 435-451 nm for NO2. The method is computationally efficient for processing OSIRIS data on an operational basis. Results show that a 2-3 km height resolution is generally achievable between about 12 km and 45 km for O3 with an estimated accuracy of 13\% at the peak and between about 15 km and 40 km for NO2 with an estimated accuracy of 10\% at the peak. First validations of the retrieved data indicate a good agreement both with other retrieval techniques applied to OSIRIS measurements and with the results of other instruments. Once the validation has reached a confident level, the retrieved data will be used to study important stratospheric processes relevant to global environmental problems. The unique NO2 data set will be of particular interest for studies of nitrogen chemistry in the middle atmosphere.
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- Levin, Johannes, et al.
(författare)
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α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 20:6, s. 4351-4365
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. Highlights: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP.
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- Morenas-Rodriguez, E., et al.
(författare)
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Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer acute accent s disease: a longitudinal observational study
- 2022
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Ingår i: LANCET NEUROLOGY. - 1474-4422. ; 21:4, s. 329-341
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Tidskriftsartikel (refereegranskat)abstract
- Background Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid beta (A beta) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease. Methods We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer's disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1 , PSEN2 , and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR > 0). CSF concentrations of A beta 40, A beta 42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models. Findings In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF A beta 42 (beta=-4.28 x 10(-2) [SE 0.013], p=0.0012), but not high cortical uptake in PiB-PET (beta=-5.51 x 10(-3) [0.011], p=0.63), was the only predictor of an augmented annual rate of subsequent increase in soluble TREM2. Augmented annual rates of increase in soluble TREM2 were associated with a diminished rate of decrease in amyloid deposition, as measured by A beta 42 in CSF (r=0.56 [0.22], p=0.011), in presymptomatic carriers of pathogenic variants, and with diminished annual rate of increase in PiB-PET (r=-0.67 [0.25], p=0.0060) in symptomatic carriers of pathogenic variants. Presymptomatic carriers of pathogenic variants with annual rates of increase in soluble TREM2 lower than the median showed a correlation between enhanced annual rates of increase in p-tau in CSF and augmented annual rates of increase in PiB-PET signal (r=0.45 [0.21], p=0.035), that was not observed in those with rates of increase in soluble TREM2 higher than the median. Furthermore, presymptomatic carriers of pathogenic variants with rates of increase in soluble TREM2 above or below the median had opposite associations between A beta 42 in CSF and PiB-PET uptake when assessed longitudinally. Augmented annual rates of increase in soluble TREM2 in presymptomatic carriers of pathogenic variants correlated with decreased cortical shrinkage in the precuneus (r=0.46 [0.22]), p=0.040) and diminished cognitive decline (r=0.67 [0.22], p=0.0020). Interpretation Our findings in autosomal dominant Alzheimer's disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in A beta aggregation and further support the role of TREM2 on A beta plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on A beta deposition, A beta-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing. Funding German Research Foundation, US National Institutes of Health.Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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- Petelina, S., et al.
(författare)
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Comparison of the Odin/OSIRIS stratospheric ozone profiles with coincident POAM III and ozonesonde measurements
- 2004
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Ingår i: Geophysical Research Letters. - 1944-8007 .- 0094-8276. ; 31:7, s. L07104-
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Tidskriftsartikel (refereegranskat)abstract
- We present first statistical comparison results for stratospheric ozone density profiles retrieved from Odin/OSIRIS limb scattered radiance with 1220 coincident POAM III and 205 coincident ozonesonde measurements. Profiles are compared on a monthly basis from November 2001 to October 2002. Most of the time, differences between OSIRIS mean profiles and those measured by POAM III and ozonesondes were 5-7% between 15 km and 32 km, and within 15% above 32 km. In April-July 2002, OSIRIS mean profiles appear shifted downward by ∼1 km, introducing a difference of about 10% with POAM III and about 25% with ozonesonde profiles between 15 km and 32 km. This study demonstrates that outside the April-July 2002 period, the OSIRIS ozone profiles agree well with coincident ozonesonde and POAM III ozone profiles and make a valuable addition to the international ozone database available for research into global ozone change.
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- Walker, Steven M, et al.
(författare)
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Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:4, s. 509-518
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation.CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential.PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.
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- Gattinger, R. L., et al.
(författare)
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Vibrational populations of near-ultraviolet O-2 band systems in the night airglow
- 2012
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Ingår i: Canadian journal of physics (Print). - : Canadian Science Publishing. - 0008-4204 .- 1208-6045. ; 90:8, s. 741-751
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Tidskriftsartikel (refereegranskat)abstract
- Observations of the limb night airglow spectrum from 250 to 475 nm, emitted from the upper mesosphere and lower thermosphere, are compared with model spectra. Data from the Arizona GLO-1 imaging spectrograph and the OSIRIS spectrograph are combined to form the observed mean airglow spectrum; a tabulated version of this spectrum is included. Model spectra of the individual O-2 Herzberg I, II, and III, Chamberlain, and Slanger band systems are combined to simulate the observed mean spectrum. Franck-Condon relative band intensities are used to form a series of basis functions for the upper vibrational levels in each band system. These functions are fitted to the observed airglow spectrum with a least-squares method, the relative vibrational populations are derived and discussed.
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- Orr, Nick, et al.
(författare)
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Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:11, s. 1182-1184
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 x 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 x 10(-15); OR = 1.50).
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