| 1. |
|
|
| 2. |
- Smith, Jennifer A, et al.
(författare)
-
Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
-
Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
-
Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
|
|
| 3. |
- Weinhofer, Isabelle, et al.
(författare)
-
Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy.
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
|
|
| 4. |
- Andersen, Jeppe R., et al.
(författare)
-
Les Houches 2017: Physics at TeV Colliders Standard Model Working Group Report
- 2018. - 07977
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This Report summarizes the proceedings of the 2017 Les Houches workshop on Physics at TeV Colliders. Session 1 dealt with (I) new developments relevant for high precision Standard Model calculations, (II) theoretical uncertainties and dataset dependence of parton distribution functions, (III) new developments in jet substructure techniques, (IV) issues in the theoretical description of the production of Standard Model Higgs bosons and how to relate experimental measurements, (V) phenomenological studies essential for comparing LHC data from Run II with theoretical predictions and projections for future measurements, and (VI) new developments in Monte Carlo event generators.
|
|
| 5. |
- Anderson, Beverley H., et al.
(författare)
-
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 338-342
-
Tidskriftsartikel (refereegranskat)abstract
- Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
|
|
| 6. |
- Arganda-Carreras, Ignacio, et al.
(författare)
-
Crowdsourcing the creation of image segmentation algorithms for connectomics
- 2015
-
Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media S.A.. - 1662-5129. ; 9:142
-
Tidskriftsartikel (refereegranskat)abstract
- To stimulate progress in automating the reconstruction of neural circuits, we organized the first international challenge on 2D segmentation of electron microscopic (EM) images of the brain. Participants submitted boundary maps predicted for a test set of images, and were scored based on their agreement with a consensus of human expert annotations. The winning team had no prior experience with EM images, and employed a convolutional network. This "deep learning" approach has since become accepted as a standard for segmentation of FM images. The challenge has continued to accept submissions, and the best so far has resulted from cooperation between two teams. The challenge has probably saturated, as algorithms cannot progress beyond limits set by ambiguities inherent in 2D scoring and the size of the test dataset. Retrospective evaluation of the challenge scoring system reveals that it was not sufficiently robust to variations in the widths of neurite borders. We propose a solution to this problem, which should be useful for a future 3D segmentation challenge.
|
|
| 7. |
- Frazier-Wood, Alexis C., et al.
(författare)
-
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
-
Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
-
Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
|
|
| 8. |
- Gil Gómez, Gaspar, et al.
(författare)
-
Improving subjective assessments of vehicle dynamics evaluations by means of computer tablets as digital aid
- 2016
-
Ingår i: Computer software and hardware. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International.
-
Konferensbidrag (refereegranskat)abstract
- Vehicle dynamics development relies on subjective assessments (SA), which is a resource-intensive procedure requiring both expert drivers and vehicles. Furthermore, development projects becoming shorter and more complex, and increasing demands on quality require higher efficiency.Most research in this area has focused on moving from physical to virtual testing. However, SA remains the central method. Less attention has been given to provide better tools for the SA process itself. One promising approach is to introduce computer-tablets to aid data collection, which has proven to be useful in medical studies. Simple software solutions can eliminate the need to transcribe data and generate more flexible and better maintainable questionnaires. Tablets’ technical features envision promising enhancements of SA, which also enable better correlations to objective metrics, a requirement to improve CAE evaluations.However, it cannot be assumed that a tablet-based solution is feasible in vehicle dynamics SA context. Any distraction might result in low SA quality and safety issues when test-drivers are subjected to high mental workload pushing the vehicles to their performance-limits.In this study, a SA tablet-software for steering feel, handling, and ride was developed and systematically evaluated versus the traditional pen-and-paper method. The results indicate that the new approach is technically feasible in this context, meets more use-cases, and the drivers’ attitude towards it is positive. It increased questionnaire completion and rating resolution while reducing the error rate and transcription time.Although attendees reported that the paper-based approach has advantages from a usability point of view, the benefits of the tablet-based approach enable further process-related advantages.
|
|
| 9. |
- Hedin, Allan, et al.
(författare)
-
Corrosion of copper in pure O2-free water?
- 2018
-
Ingår i: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 137, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- Copper exposed to pure, O-2-free water for several months in glass- and metal-contained, well-controlled systems shows no evidence of corrosion, either through hydrogen evolution or through the occurrence of oxidized copper. The results contradict the interpretation of recent experiments where it has been claimed that copper corrodes in pure, O-2-free water far above the very limited extent predicted by established thermodynamic data. Reasons for the different experimental outcomes are discussed. Experimental and theoretical efforts to identify hitherto unknown, potentially corrosion driving species of the Cu-O-H system and studies of copper/water surface reactions are reviewed as background for the present study.
|
|
| 10. |
- Jewell, Jessica, 1982, et al.
(författare)
-
Reply to: Why fossil fuel producer subsidies matter
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. E5-E7
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
