| 1. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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| 8. |
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| 9. |
- Rajewsky, N., et al.
(author)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Journal article (peer-reviewed)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 10. |
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| 11. |
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| 12. |
- Dahl-Jensen, D., et al.
(author)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Journal article (peer-reviewed)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 13. |
- Abolfathi, Bela, et al.
(author)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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In: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Journal article (peer-reviewed)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 14. |
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| 15. |
- Blanton, Michael R., et al.
(author)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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In: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Journal article (peer-reviewed)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 16. |
- Hong, S. J., et al.
(author)
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TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels
- 2021
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:10, s. 1628-1640
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Journal article (peer-reviewed)abstract
- Introduction Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Methods We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates. Results We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1. Discussion Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.
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| 17. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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In: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Journal article (peer-reviewed)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 18. |
- Smith, P., et al.
(author)
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How much land-based greenhouse gas mitigation can be achieved without compromising food security and environmental goals?
- 2013
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In: Global Change Biology. - : Wiley. - 1365-2486 .- 1354-1013. ; 19:8, s. 2285-2302
-
Research review (peer-reviewed)abstract
- Feeding 9-10billion people by 2050 and preventing dangerous climate change are two of the greatest challenges facing humanity. Both challenges must be met while reducing the impact of land management on ecosystem services that deliver vital goods and services, and support human health and well-being. Few studies to date have considered the interactions between these challenges. In this study we briefly outline the challenges, review the supply- and demand-side climate mitigation potential available in the Agriculture, Forestry and Other Land Use AFOLU sector and options for delivering food security. We briefly outline some of the synergies and trade-offs afforded by mitigation practices, before presenting an assessment of the mitigation potential possible in the AFOLU sector under possible future scenarios in which demand-side measures codeliver to aid food security. We conclude that while supply-side mitigation measures, such as changes in land management, might either enhance or negatively impact food security, demand-side mitigation measures, such as reduced waste or demand for livestock products, should benefit both food security and greenhouse gas (GHG) mitigation. Demand-side measures offer a greater potential (1.5-15.6Gt CO2-eq. yr(-1)) in meeting both challenges than do supply-side measures (1.5-4.3Gt CO2-eq. yr(-1) at carbon prices between 20 and 100US$ tCO(2)-eq. yr(-1)), but given the enormity of challenges, all options need to be considered. Supply-side measures should be implemented immediately, focussing on those that allow the production of more agricultural product per unit of input. For demand-side measures, given the difficulties in their implementation and lag in their effectiveness, policy should be introduced quickly, and should aim to codeliver to other policy agenda, such as improving environmental quality or improving dietary health. These problems facing humanity in the 21st Century are extremely challenging, and policy that addresses multiple objectives is required now more than ever.
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| 19. |
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| 20. |
- Aguado, D. S., et al.
(author)
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The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
- 2019
-
In: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
-
Journal article (peer-reviewed)abstract
- Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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| 21. |
- Bos, I., et al.
(author)
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Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum
- 2019
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:5, s. 644-654
-
Journal article (peer-reviewed)abstract
- Introduction: We investigated relations between amyloid-beta (A beta) status, apolipoprotein E (APOE) e4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau). Methods: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with A beta status (Ab beta- vs. A beta+), clinical diagnosis APOE epsilon 4 carriership, baseline cognition, and change in cognition. Results: Ng and T-tau distinguished between A beta+ from A beta- individuals in each clinical group, whereas NFL and YKL-40 were associated with A beta+ in nondemented individuals only. APOE epsilon 4 carriership did not influence NFL, Ng, and YKL-40 in A beta+ individuals. NFL was the best predictor of cognitive decline in A beta+ individuals across the cognitive spectrum. Discussion: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 22. |
- Jansen, Willemijn J, et al.
(author)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
-
Journal article (peer-reviewed)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 23. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
-
Journal article (peer-reviewed)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 24. |
- Jansen, Willemijn J, et al.
(author)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Journal article (peer-reviewed)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 25. |
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| 26. |
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| 27. |
- Langer, Judith, et al.
(author)
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Present and Future of Surface-Enhanced Raman Scattering
- 2020
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 14:1, s. 28-117
-
Research review (peer-reviewed)abstract
- The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article. ©
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| 28. |
- Mattsson, Niklas, et al.
(author)
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Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
- 2018
-
In: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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| 29. |
- Mattsson, Niklas, et al.
(author)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
-
In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
-
Journal article (peer-reviewed)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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| 30. |
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| 31. |
- Santee, M.L., et al.
(author)
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Validation of the Aura Microwave Limb Sounder HNO3 Measurements
- 2007
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 112:D24
-
Journal article (peer-reviewed)abstract
- [1] We assess the quality of the version 2.2 (v2.2) HNO(3) measurements from the Microwave Limb Sounder (MLS) on the Earth Observing System Aura satellite. The MLS HNO(3) product has been greatly improved over that in the previous version (v1.5), with smoother profiles, much more realistic behavior at the lowest retrieval levels, and correction of a high bias caused by an error in one of the spectroscopy files used in v1.5 processing. The v2.2 HNO(3) data are scientifically useful over the range 215 to 3.2 hPa, with single-profile precision of similar to 0.7 ppbv throughout. Vertical resolution is 3-4 km in the upper troposphere and lower stratosphere, degrading to similar to 5 km in the middle and upper stratosphere. The impact of various sources of systematic uncertainty has been quantified through a comprehensive set of retrieval simulations. In aggregate, systematic uncertainties are estimated to induce in the v2.2 HNO(3) measurements biases that vary with altitude between +/- 0.5 and +/- 2 ppbv and multiplicative errors of +/- 5-15% throughout the stratosphere, rising to similar to +/- 30% at 215 hPa. Consistent with this uncertainty analysis, comparisons with correlative data sets show that relative to HNO(3) measurements from ground- based, balloon- borne, and satellite instruments operating in both the infrared and microwave regions of the spectrum, MLS v2.2 HNO(3) mixing ratios are uniformly low by 10-30% throughout most of the stratosphere. Comparisons with in situ measurements made from the DC-8 and WB-57 aircraft in the upper troposphere and lowermost stratosphere indicate that the MLS HNO(3) values are low in this region as well, but are useful for scientific studies (with appropriate averaging).
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| 32. |
- Sguazzin, M., et al.
(author)
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Determining neutron-induced reaction cross sections through surrogate reactions at storage rings
- 2023
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In: Journal of Physics: Conference Series. - 1742-6588 .- 1742-6596. ; 2586:1
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Conference paper (peer-reviewed)abstract
- Determining the cross sections of neutron-induced reactions on short-lived nuclei is imperative to rate calculations in stellar nucleosynthesis and applications of nuclear physics. It is also an immense experimental challenge due to the radioactivity of the targets involved. Our goal is to circumvent this obstacle by using surrogate reactions in inverse kinematics at the heavy-ion storage rings of GSI/FAIR. We present here preliminary results from the first proof of principle experiment, where a beam of 208Pb impinged on a H2 gas jet target in the Experimental Storage Ring (ESR).
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| 33. |
- Sguazzin, M., et al.
(author)
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Indirect measurements of neutron -induced reaction cross sections at heavy -ion storage rings
- 2023
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In: 15TH INTERNATIONAL CONFERENCE ON NUCLEAR DATA FOR SCIENCE AND TECHNOLOGY, ND2022. - 2100-014X. ; 284
-
Conference paper (peer-reviewed)abstract
- Neutron-induced reaction cross sections of unstable nuclei are essential for understanding the synthesis of heavy elements in stars and for applications in nuclear technology. However, their measurement is very complicated due to the radioactivity of the targets involved. We propose to circumvent this problem by using the surrogate reaction method in inverse kinematics, where the nucleus formed in the neutroninduced reaction of interest is produced by a reaction involving a radioactive heavy -ion beam and a stable, light target nucleus. The probabilities as a function of the compound -nucleus excitation energy for y -ray emission, neutron emission and fission, which can be measured with the surrogate reaction, are particularly useful to constrain model parameters and to obtain more accurate predictions of the neutron-induced reaction cross sections of interest. Yet, the full development of the surrogate method is hampered by numerous longstanding target issues, which can be solved by combining surrogate reactions with the unique and largely unexplored possibilities at heavy -ion storage rings. In this contribution, we describe the developments we are carrying out to measure for the first time simultaneously y-ray emission, neutron emission and fission probabilities at the storage rings of the GSI/FAIR facility. In particular, we will present the first results of the proof of principle experiment, which we performed in June 2022 at the Experimental Storage Ring (ESR)
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| 34. |
- Sguazzin, M., et al.
(author)
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Indirect measurements of neutron-induced reaction cross sections at storage rings
- 2023
-
In: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
-
Conference paper (peer-reviewed)abstract
- Neutron-induced reaction cross sections of unstable nuclei are essential for understanding the synthesis of heavy elements in stars. However, their measurement is very difficult due to the radioactivity of the targets involved. We propose to circumvent this problem by using for the first time the surrogate reaction method in inverse kinematics at heavy-ion storage rings. In this contribution, we describe the developments we have done to perform surrogate-reaction studies at the storage rings of GSI/FAIR. In particular, we present the first results of the proof of principle experiment, which we conducted recently at the Experimental Storage Ring (ESR).
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| 35. |
- Steen-Larsen, H. C., et al.
(author)
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Continuous monitoring of summer surface water vapor isotopic composition above the Greenland Ice Sheet
- 2013
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7324. ; 13:9, s. 4815-4828
-
Journal article (peer-reviewed)abstract
- We present here surface water vapor isotopic measurements conducted from June to August 2010 at the NEEM (North Greenland Eemian Drilling Project) camp, NW Greenland (77.45 degrees N, 51.05 degrees W, 2484 m a.s.l.). Measurements were conducted at 9 different heights from 0.1m to 13.5m above the snow surface using two different types of cavity-enhanced near-infrared absorption spectroscopy analyzers. For each instrument specific protocols were developed for calibration and drift corrections. The inter-comparison of corrected results from different instruments reveals excellent reproducibility, stability, and precision with a standard deviations of similar to 0.23 parts per thousand for delta O-18 and similar to 1.4 parts per thousand for delta D. Diurnal and intraseasonal variations show strong relationships between changes in local surface humidity and water vapor isotopic composition, and with local and synoptic weather conditions. This variability probably results from the interplay between local moisture fluxes, linked with firn-air exchanges, boundary layer dynamics, and large-scale moisture advection. Particularly remarkable are several episodes characterized by high (> 40 parts per thousand) surface water vapor deuterium excess. Air mass back-trajectory calculations from atmospheric analyses and water tagging in the LMDZiso (Laboratory of Meteorology Dynamics Zoom-isotopic) atmospheric model reveal that these events are associated with predominant Arctic air mass origin. The analysis suggests that high deuterium excess levels are a result of strong kinetic fractionation during evaporation at the sea-ice margin.
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| 36. |
- ten Kate, M., et al.
(author)
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MRI predictors of amyloid pathology: results from the EMIF-AD Multimodal Biomarker Discovery study
- 2018
-
In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
-
Journal article (peer-reviewed)abstract
- Background: With the shift of research focus towards the pre-dementia stage of Alzheimer's disease (AD), there is an urgent need for reliable, non-invasive biomarkers to predict amyloid pathology. The aim of this study was to assess whether easily obtainable measures from structural MRI, combined with demographic data, cognitive data and apolipoprotein E (APOE) epsilon 4 genotype, can be used to predict amyloid pathology using machine-learning classification. Methods: We examined 810 subjects with structural MRI data and amyloid markers from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, including subjects with normal cognition (CN, n = 337, age 66.5 +/- 72, 50% female, 27% amyloid positive), mild cognitive impairment (MCI, n = 375, age 69. 1 +/- 7.5, 53% female, 63% amyloid positive) and AD dementia (n = 98, age 67.0 +/- 7.7, 48% female, 97% amyloid positive). Structural MRI scans were visually assessed and Freesurfer was used to obtain subcortical volumes, cortical thickness and surface area measures. We first assessed univariate associations between MRI measures and amyloid pathology using mixed models. Next, we developed and tested an automated classifier using demographic, cognitive, MRI and APOE epsilon 4 information to predict amyloid pathology. A support vector machine (SVM) with nested 10-fold cross-validation was applied to identify a set of markers best discriminating between amyloid positive and amyloid negative subjects. Results: In univariate associations, amyloid pathology was associated with lower subcortical volumes and thinner cortex in AD-signature regions in CN and MCI. The multi-variable SVM classifier provided an area under the curve (AUC) of 0.81 +/- O. 07 in MCI and an AUC of 0.74 +/- 0.08 in CN. In CN, selected features for the classifier included APOE epsilon 4, age, memory scores and several MRI measures such as hippocampus, amygdala and accumbens volumes and cortical thickness in temporal and parahippocampal regions. In MCI, the classifier including demographic and APOE epsilon 4 information did not improve after additionally adding imaging measures. Conclusions: Amyloid pathology is associated with changes in structural MRI measures in CN and MCI. An automated classifier based on clinical, imaging and APOE epsilon 4 data can identify the presence of amyloid pathology with a moderate level of accuracy. These results could be used in clinical trials to pre-screen subjects for anti-amyloid therapies.
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| 37. |
- Bos, I., et al.
(author)
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The EMIF-AD Multimodal Biomarker Discovery study: design, methods and cohort characteristics
- 2018
-
In: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10
-
Journal article (peer-reviewed)abstract
- Background: There is an urgent need for novel, noninvasive biomarkers to diagnose Alzheimer's disease (AD) in the predementia stages and to predict the rate of decline. Therefore, we set up the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study. In this report we describe the design of the study, the methods used and the characteristics of the participants. Methods: Participants were selected from existing prospective multicenter and single-center European studies. Inclusion criteria were having normal cognition (NC) or a diagnosis of mild cognitive impairment (MCI) or AD-type dementia at baseline, age above 50 years, known amyloid-beta (A beta) status, availability of cognitive test results and at least two of the following materials: plasma, DNA, magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF). Targeted and untargeted metabolomic and proteomic analyses were performed in plasma, and targeted and untargeted proteomics were performed in CSF. Genome-wide SNP genotyping, next-generation sequencing and methylation profiling were conducted in DNA. Visual rating and volumetric measures were assessed on MRI. Baseline characteristics were analyzed using ANOVA or chi-square, rate of decline analyzed by linear mixed modeling. Results: We included 1221 individuals (NC n = 492, MCI n = 527, AD-type dementia n = 202) with a mean age of 67.9 (SD 8.3) years. The percentage A beta+ was 26% in the NC, 58% in the MCI, and 87% in the AD-type dementia groups. Plasma samples were available for 1189 (97%) subjects, DNA samples for 929 (76%) subjects, MRI scans for 862 (71%) subjects and CSF samples for 767 (63%) subjects. For 759 (62%) individuals, clinical follow-up data were available. In each diagnostic group, the APOE e4 allele was more frequent amongst A beta+ individuals (p < 0.001). Only in MCI was there a difference in baseline Mini Mental State Examination (MMSE) score between the A groups (p< 0.001). A beta+ had a faster rate of decline on the MMSE during follow-up in the NC (p < 0.001) and MCI (p < 0.001) groups. Conclusions: The characteristics of this large cohort of elderly subjects at various cognitive stages confirm the central roles of A beta and APOE epsilon 4 in AD pathogenesis. The results of the multimodal analyses will provide new insights into underlying mechanisms and facilitate the discovery of new diagnostic and prognostic AD biomarkers. All researchers can apply for access to the EMIF-AD MBD data by submitting a research proposal via the EMIF-AD Catalog.
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| 38. |
- Gizaw, A., et al.
(author)
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Colonization and diversification in the African 'sky islands': insights from fossil-calibrated molecular dating of Lychnis (Caryophyllaceae)
- 2016
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 211:2, s. 719-734
-
Journal article (peer-reviewed)abstract
- The flora on the isolated high African mountains or 'sky islands' is remarkable for its peculiar adaptations, local endemism and striking biogeographical connections to remote parts of the world. Ages of the plant lineages and the timing of their radiations have frequently been debated but remain contentious as there are few estimates based on explicit models and fossil-calibrated molecular clocks. We used the plastid region maturaseK (matK) and a Caryophylloflora paleogenica fossil to infer the age of the genus Lychnis, and constructed a data set of three plastid (matK; a ribosomal protein S16 (rps16); and an intergenic spacer (psbE-petL)) and two nuclear (internal transcribed spacer (ITS) and a region spanning exon 18-24 in the second largest subunit of RNA polymerase II (RPB2)) loci for joint estimation of the species tree and divergence time of the African representatives. The time of divergence of the African high-altitude Lychnis was placed in the late Miocene to early Pliocene. A single speciation event was inferred in the early Pliocene; subsequent speciation took place sporadically from the late Pliocene to the middle Pleistocene. We provide further support for a Eurasian origin of the African 'sky islands' floral elements, which seem to have been recruited via dispersals at different times: some old, as in Lychnis, and others very recent. We show that dispersal and diversification within Africa play an important role in shaping these isolated plant communities.
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| 39. |
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| 40. |
- Janssen, O., et al.
(author)
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Characteristics of subjective cognitive decline associated with amyloid positivity
- 2022
-
In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:10, s. 1832-1845
-
Journal article (peer-reviewed)abstract
- Introduction The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. Methods In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) epsilon 4 carriership, and neuropsychiatric symptoms with amyloid positivity. Results Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE epsilon 4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. Discussion Next to age, setting, and APOE epsilon 4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.
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| 41. |
- Kim, HyeJin, et al.
(author)
-
Towards a better future for biodiversity and people : Modelling Nature Futures
- 2023
-
In: Global Environmental Change. - 0959-3780 .- 1872-9495. ; 82
-
Journal article (peer-reviewed)abstract
- The Nature Futures Framework (NFF) is a heuristic tool for co-creating positive futures for nature and people. It seeks to open up a diversity of futures through mainly three value perspectives on nature - Nature for Nature, Nature for Society, and Nature as Culture. This paper describes how the NFF can be applied in modelling to support decision-making. First, we describe key considerations for the NFF in developing qualitative and quantitative scenarios: i) multiple value perspectives on nature as a state space where pathways improving nature toward a frontier can be represented, ii) mutually reinforcing key feedbacks of social-ecological systems that are important for nature conservation and human wellbeing, iii) indicators of multiple knowledge systems describing the evolution of complex social-ecological dynamics. We then present three approaches to modelling Nature Futures scenarios in the review, screening, and design phases of policy processes. This paper seeks to facilitate the integration of relational values of nature in models and strengthen modelled linkages across biodiversity, nature's contributions to people, and quality of life.
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| 42. |
- Neumann, A., et al.
(author)
-
Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer's disease CSF profile of neuronal injury and inflammation
- 2022
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27, s. 1990-1999
-
Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (beta-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on NfL and YKL-40, indicators of neuronal injury and inflammation. Four genes were associated with this PC: IFFO1, DTNB, NLRC3, and SLC22A10. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2 and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB, NLRC3, and SLC22A10 heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2 and CASZ1 were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.
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| 43. |
- Robledo-Abad, Carmenza, et al.
(author)
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Bioenergy production and sustainable development: science base for policy-making remains limited
- 2017
-
In: Global Change Biology Bioenergy. - : Wiley. - 1757-1693 .- 1757-1707. ; 9:3, s. 541-556
-
Journal article (peer-reviewed)abstract
- The possibility of using bioenergy as a climate change mitigation measure has sparked a discussion of whether and how bioenergy production contributes to sustainable development. We undertook a systematic review of the scientific literature to illuminate this relationship and found a limited scientific basis for policy-making. Our results indicate that knowledge on the sustainable development impacts of bioenergy production is concentrated in a few well-studied countries, focuses on environmental and economic impacts, and mostly relates to dedicated agricultural biomass plantations. The scope and methodological approaches in studies differ widely and only a small share of the studies sufficiently reports on context and/or baseline conditions, which makes it difficult to get a general understanding of the attribution of impacts. Nevertheless we identified regional patterns of positive or negative impacts for all categories – environmental, economic, institutional, social and technological. In general, economic and technological impacts were more frequently reported as positive, while social and environmental impacts were more frequently reported as negative (with the exception of impacts on direct substitution of GHG emission from fossil fuel). More focused and transparent research is needed to validate these patterns and develop a strong science underpinning for establishing policies and governance agreements that prevent/mitigate negative and promote positive impacts from bioenergy production.
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| 44. |
- Shi, L., et al.
(author)
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Multiomics profiling of human plasma and cerebrospinal fluid reveals ATN-derived networks and highlights causal links in Alzheimer's disease
- 2023
-
In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:8, s. 3359-3364
-
Journal article (peer-reviewed)abstract
- IntroductionThis study employed an integrative system and causal inference approach to explore molecular signatures in blood and CSF, the amyloid/tau/neurodegeneration [AT(N)] framework, mild cognitive impairment (MCI) conversion to Alzheimer's disease (AD), and genetic risk for AD. MethodsUsing the European Medical Information Framework (EMIF)-AD cohort, we measured 696 proteins in cerebrospinal fluid (n = 371), 4001 proteins in plasma (n = 972), 611 metabolites in plasma (n = 696), and genotyped whole-blood (7,778,465 autosomal single nucleotide epolymorphisms, n = 936). We investigated associations: molecular modules to AT(N), module hubs with AD Polygenic Risk scores and APOE4 genotypes, molecular hubs to MCI conversion and probed for causality with AD using Mendelian randomization (MR). ResultsAT(N) framework associated with protein and lipid hubs. In plasma, Proprotein Convertase Subtilisin/Kexin Type 7 showed evidence for causal associations with AD. AD was causally associated with Reticulocalbin 2 and sphingomyelins, an association driven by the APOE isoform. DiscussionThis study reveals multi-omics networks associated with AT(N) and causal AD molecular candidates.
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| 45. |
- Shi, Liu, et al.
(author)
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Replication study of plasma proteins relating to Alzheimer's pathology.
- 2021
-
In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279 .- 1552-5260. ; 17:9, s. 1452-1464
-
Journal article (peer-reviewed)abstract
- This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis.Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively.Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis.Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.
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| 46. |
- Alexander, Peter, et al.
(author)
-
Assessing uncertainties in land cover projections
- 2017
-
In: Global Change Biology. - : Wiley. - 1354-1013. ; 23:2, s. 767-781
-
Journal article (peer-reviewed)abstract
- Understanding uncertainties in land cover projections is critical to investigating land-based climate mitigation policies, assessing the potential of climate adaptation strategies and quantifying the impacts of land cover change on the climate system. Here, we identify and quantify uncertainties in global and European land cover projections over a diverse range of model types and scenarios, extending the analysis beyond the agro-economic models included in previous comparisons. The results from 75 simulations over 18 models are analysed and show a large range in land cover area projections, with the highest variability occurring in future cropland areas. We demonstrate systematic differences in land cover areas associated with the characteristics of the modelling approach, which is at least as great as the differences attributed to the scenario variations. The results lead us to conclude that a higher degree of uncertainty exists in land use projections than currently included in climate or earth system projections. To account for land use uncertainty, it is recommended to use a diverse set of models and approaches when assessing the potential impacts of land cover change on future climate. Additionally, further work is needed to better understand the assumptions driving land use model results and reveal the causes of uncertainty in more depth, to help reduce model uncertainty and improve the projections of land cover.
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| 47. |
- Brändén, Gisela, 1975, et al.
(author)
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Coherent diffractive imaging of microtubules using an X-ray laser.
- 2019
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
-
Journal article (peer-reviewed)abstract
- X-ray free electron lasers (XFELs) create new possibilities for structural studies of biological objects that extend beyond what is possible with synchrotron radiation. Serial femtosecond crystallography has allowed high-resolution structures to be determined from micro-meter sized crystals, whereas single particle coherent X-ray imaging requires development to extend the resolution beyond a few tens of nanometers. Here we describe an intermediate approach: the XFEL imaging of biological assemblies with helical symmetry. We collected X-ray scattering images from samples of microtubules injected across an XFEL beam using a liquid microjet, sorted these images into class averages, merged these data into a diffraction pattern extending to 2nm resolution, and reconstructed these data into a projection image of the microtubule. Details such as the 4nm tubulin monomer became visible in this reconstruction. These results illustrate the potential of single-molecule X-ray imaging of biological assembles with helical symmetry at room temperature.
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| 48. |
- Chernenkaya, A., et al.
(author)
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Microscopic origin of the charge transfer in single crystals based on thiophene derivatives : A combined NEXAFS and density functional theory approach
- 2016
-
In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 145:3
-
Journal article (peer-reviewed)abstract
- We have investigated the charge transfer mechanism in single crystals of DTBDT-TCNQ and DTBDT-F4TCNQ (where DTBDT is dithieno[2,3-d;2′,3′-d′] benzo[1,2-b;4,5-b′]dithiophene) using a combination of near-edge X-ray absorption spectroscopy (NEXAFS) and density functional theory calculations (DFT) including final state effects beyond the sudden state approximation. In particular, we find that a description that considers the partial screening of the electron-hole Coulomb correlation on a static level as well as the rearrangement of electronic density shows excellent agreement with experiment and allows to uncover the details of the charge transfer mechanism in DTBDT-TCNQ and DTBDT-F4 TCNQ, as well as a reinterpretation of previous NEXAFS data on pure TCNQ. Finally, we further show that almost the same quality of agreement between theoretical results and experiment is obtained by the much faster Z+1/2 approximation, where the core hole effects are simulated by replacing N or F with atomic number Z with the neighboring atom with atomic number Z+1/2.
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| 49. |
- Creutzig, F., et al.
(author)
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Bioenergy and climate change mitigation: an assessment
- 2015
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In: GCB Bioenergy. - : Wiley. - 1757-1707 .- 1757-1693. ; 7:5, s. 916-944
-
Research review (peer-reviewed)abstract
- Bioenergy deployment offers significant potential for climate change mitigation, but also carries considerable risks. In this review, we bring together perspectives of various communities involved in the research and regulation of bioenergy deployment in the context of climate change mitigation: Land-use and energy experts, land-use and integrated assessment modelers, human geographers, ecosystem researchers, climate scientists and two different strands of life-cycle assessment experts. We summarize technological options, outline the state-of-the-art knowledge on various climate effects, provide an update on estimates of technical resource potential and comprehensively identify sustainability effects. Cellulosic feedstocks, increased end-use efficiency, improved land carbon-stock management and residue use, and, when fully developed, BECCS appear as the most promising options, depending on development costs, implementation, learning, and risk management. Combined heat and power, efficient biomass cookstoves and small-scale power generation for rural areas can help to promote energy access and sustainable development, along with reduced emissions. We estimate the sustainable technical potential as up to 100EJ: high agreement; 100-300EJ: medium agreement; above 300EJ: low agreement. Stabilization scenarios indicate that bioenergy may supply from 10 to 245EJyr(-1) to global primary energy supply by 2050. Models indicate that, if technological and governance preconditions are met, large-scale deployment (>200EJ), together with BECCS, could help to keep global warming below 2 degrees degrees of preindustrial levels; but such high deployment of land-intensive bioenergy feedstocks could also lead to detrimental climate effects, negatively impact ecosystems, biodiversity and livelihoods. The integration of bioenergy systems into agriculture and forest landscapes can improve land and water use efficiency and help address concerns about environmental impacts. We conclude that the high variability in pathways, uncertainties in technological development and ambiguity in political decision render forecasts on deployment levels and climate effects very difficult. However, uncertainty about projections should not preclude pursuing beneficial bioenergy options.
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| 50. |
- Delvenne, A., et al.
(author)
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Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer's disease pathophysiology
- 2023
-
In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:3, s. 807-820
-
Journal article (peer-reviewed)abstract
- Background Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics. Methods Individuals were classified based on CSF amyloid beta (A beta)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed. Results A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus. Conclusion The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD.
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