| 1. |
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| 2. |
- Aaron, F. D., et al.
(author)
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Events with an isolated lepton and missing transverse momentum and measurement of W production at HERA
- 2010
-
In: Journal of High Energy Physics. - 1029-8479. ; 2010:3, s. 1-19
-
Journal article (peer-reviewed)abstract
- A search for events containing an isolated electron or muon and missing trans verse momentum produced in e(+/-)p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb(-1). The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e(+)p data, at large hadronic transverse momentum P-T(X) > 25GeV, a total of 23 events are observed compared to a prediction of 14.0 +/- 1.9. The total single W boson production cross section is measured as 1.06 +/- 0.16 (stat.) +/- 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 +/- 0.19 pb.
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| 3. |
- Aaron, F. D., et al.
(author)
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Multi-leptons with high transverse momentum at HERA
- 2009
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In: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
-
Journal article (peer-reviewed)abstract
- Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
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| 4. |
- Aaron, F. D., et al.
(author)
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Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA
- 2010
-
In: Journal of High Energy Physics. - 1029-8479. ; :1
-
Journal article (peer-reviewed)abstract
- A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.
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| 5. |
- Aaron, F. D., et al.
(author)
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Combined inclusive diffractive cross sections measured with forward proton spectrometers in deep inelastic ep scattering at HERA
- 2012
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 72:10
-
Journal article (peer-reviewed)abstract
- A combination of the inclusive diffractive cross section measurements made by the H1 and ZEUS Collaborations at HERA is presented. The analysis uses samples of diffractive deep inelastic ep scattering data at a centre-of-mass energy root s = 318 GeV where leading protons are detected by dedicated spectrometers. Correlations of systematic uncertainties are taken into account, resulting in an improved precision of the cross section measurement which reaches 6 % for the most precise points. The combined data cover the range 2.5 < Q(2) < 200 GeV2 in photon virtuality, 0.00035 < x(P) < 0.09 in proton fractional momentum loss, 0.09 < vertical bar t vertical bar < 0.55 GeV2 in squared four-momentum transfer at the proton vertex and 0.0018 < beta < 0.816 in beta = x/x(P), where x is the Bjorken scaling variable.
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| 6. |
- Abramowicz, H., et al.
(author)
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Combination and QCD analysis of charm production cross section measurements in deep-inelastic ep scattering at HERA
- 2013
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:2
-
Journal article (peer-reviewed)abstract
- Measurements of open charm production cross sections in deep-inelastic ep scattering at HERA from the H1 and ZEUS Collaborations are combined. Reduced cross sections sigma(c (c) over bar)(red) for charm production are obtained in the kinematic range of photon virtuality 2.5 <= Q(2) <= 2000 GeV2 and Bjorken scaling variable 3 . 10(-5) <= x <= 5 . 10(-2). The combination method accounts for the correlations of the systematic uncertainties among the different data sets. The combined charm data together with the combined inclusive deep-inelastic scattering cross sections from HERA are used as input for a detailed NLO QCD analysis to study the influence of different heavy flavour schemes on the parton distribution functions. The optimal values of the charm mass as a parameter in these different schemes are obtained. The implications on the NLO predictions for W-+/- and Z production cross sections at the LHC are investigated. Using the fixed flavour number scheme, the running mass of the charm quark is determined.
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| 7. |
- Cossarizza, A., et al.
(author)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
-
Journal article (peer-reviewed)abstract
- These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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| 8. |
- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
-
In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
-
Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 9. |
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| 10. |
- Flannick, Jason, et al.
(author)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
-
In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Journal article (peer-reviewed)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 11. |
- Fuchsberger, Christian, et al.
(author)
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The genetic architecture of type 2 diabetes
- 2016
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
-
Journal article (peer-reviewed)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 12. |
- Rheinbay, E, et al.
(author)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
-
Journal article (peer-reviewed)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 13. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 14. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
-
Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 15. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 16. |
- Ahearn, Thomas U., et al.
(author)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
-
In: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
-
Journal article (peer-reviewed)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 17. |
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| 18. |
- Mueller, Stefanie H., et al.
(author)
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Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
- 2023
-
In: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
-
Journal article (peer-reviewed)abstract
- Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
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| 19. |
- Menkveld, Albert J., et al.
(author)
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Nonstandard Errors
- 2024
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In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
Journal article (peer-reviewed)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 20. |
- Verra, L., et al.
(author)
-
Controlled Growth of the Self-Modulation of a Relativistic Proton Bunch in Plasma
- 2022
-
In: Physical Review Accelerators and Beams. - : American Physical Society. - 2469-9888. ; 25:7
-
Journal article (peer-reviewed)abstract
- A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self -modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.
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| 21. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 22. |
- Nechaeva, T., et al.
(author)
-
Hosing of a Long Relativistic Particle Bunch in Plasma
- 2024
-
In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 132:7
-
Journal article (peer-reviewed)abstract
- Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, selfmodulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma -based accelerators and represent the first characterization of hosing.
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| 23. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
-
Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 24. |
- Verra, L., et al.
(author)
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Development of the self-modulation instability of a relativistic proton bunch in plasma
- 2023
-
In: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 30:8
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Journal article (peer-reviewed)abstract
- Self-modulation is a beam-plasma instability that is useful to drive large-amplitude wakefields with bunches much longer than the plasma skin depth. We present experimental results showing that, when increasing the ratio between the initial transverse size of the bunch and the plasma skin depth, the instability occurs later along the bunch, or not at all, over a fixed plasma length because the amplitude of the initial wakefields decreases. We show cases for which self-modulation does not develop, and we introduce a simple model discussing the conditions for which it would not occur after any plasma length. Changing bunch size and plasma electron density also changes the growth rate of the instability. We discuss the impact of these results on the design of a particle accelerator based on the self-modulation instability seeded by a relativistic ionization front, such as the future upgrade of the Advanced WAKefield Experiment.
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| 25. |
- Anney, Richard, et al.
(author)
-
A genome-wide scan for common alleles affecting risk for autism.
- 2010
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
-
Journal article (peer-reviewed)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 26. |
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| 27. |
- Thompson, EJ, et al.
(author)
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Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 3528-
-
Journal article (peer-reviewed)abstract
- The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.
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| 28. |
- Abramowicz, H., et al.
(author)
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Conceptual design report for the LUXE experiment
- 2021
-
In: European Physical Journal-Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 230:11, s. 2445-2560
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Journal article (peer-reviewed)abstract
- This Conceptual Design Report describes LUXE (Laser Und XFEL Experiment), an experimental campaign that aims to combine the high-quality and high-energy electron beam of the European XFEL with a powerful laser to explore the uncharted terrain of quantum electrodynamics characterised by both high energy and high intensity. We will reach this hitherto inaccessible regime of quantum physics by analysing high-energy electron-photon and photon-photon interactions in the extreme environment provided by an intense laser focus. The physics background and its relevance are presented in the science case which in turn leads to, and justifies, the ensuing plan for all aspects of the experiment: Our choice of experimental parameters allows (i) field strengths to be probed where the coupling to charges becomes non-perturbative and (ii) a precision to be achieved that permits a detailed comparison of the measured data with calculations. In addition, the high photon flux predicted will enable a sensitive search for new physics beyond the Standard Model. The initial phase of the experiment will employ an existing 40 TW laser, whereas the second phase will utilise an upgraded laser power of 350 TW. All expectations regarding the performance of the experimental set-up as well as the expected physics results are based on detailed numerical simulations throughout.
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| 29. |
- Anney, Richard, et al.
(author)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
-
Journal article (peer-reviewed)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 30. |
- Axelson, Olav, 1937-, et al.
(author)
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Regulatory toxicology and pharmacology.
- 2003
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In: International journal of occupational and environmental health. - 1077-3525 .- 2049-3967. ; 9, s. 386-389
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Journal article (peer-reviewed)
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| 31. |
- Casey, Jillian P, et al.
(author)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
-
Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 32. |
- Kasliwal, Mansi M., et al.
(author)
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Kilonova Luminosity Function Constraints Based on Zwicky Transient Facility Searches for 13 Neutron Star Merger Triggers during O3
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:2
-
Journal article (peer-reviewed)abstract
- We present a systematic search for optical counterparts to 13 gravitational wave (GW) triggers involving at least one neutron star during LIGO/Virgo's third observing run (O3). We searched binary neutron star (BNS) and neutron star black hole (NSBH) merger localizations with the Zwicky Transient Facility (ZTF) and undertook follow-up with the Global Relay of Observatories Watching Transients Happen (GROWTH) collaboration. The GW triggers had a median localization area of 4480 deg(2), a median distance of 267 Mpc, and false-alarm rates ranging from 1.5 to 10(-25) yr(-1). The ZTF coverage in the g and r bands had a median enclosed probability of 39%, median depth of 20.8 mag, and median time lag between merger and the start of observations of 1.5 hr. The O3 follow-up by the GROWTH team comprised 340 UltraViolet/Optical/InfraRed (UVOIR) photometric points, 64 OIR spectra, and three radio images using 17 different telescopes. We find no promising kilonovae (radioactivity-powered counterparts), and we show how to convert the upper limits to constrain the underlying kilonova luminosity function. Initially, we assume that all GW triggers are bona fide astrophysical events regardless of false-alarm rate and that kilonovae accompanying BNS and NSBH mergers are drawn from a common population; later, we relax these assumptions. Assuming that all kilonovae are at least as luminous as the discovery magnitude of GW170817 (-16.1 mag), we calculate that our joint probability of detecting zero kilonovae is only 4.2%. If we assume that all kilonovae are brighter than -16.6 mag (the extrapolated peak magnitude of GW170817) and fade at a rate of 1 mag day(-1) (similar to GW170817), the joint probability of zero detections is 7%. If we separate the NSBH and BNS populations based on the online classifications, the joint probability of zero detections, assuming all kilonovae are brighter than -16.6 mag, is 9.7% for NSBH and 7.9% for BNS mergers. Moreover, no more than <57% (<89%) of putative kilonovae could be brighter than -16.6 mag assuming flat evolution (fading by 1 mag day(-1)) at the 90% confidence level. If we further take into account the online terrestrial probability for each GW trigger, we find that no more than <68% of putative kilonovae could be brighter than -16.6 mag. Comparing to model grids, we find that some kilonovae must have M-ej M, X-lan > 10(-4), or > 30 degrees to be consistent with our limits. We look forward to searches in the fourth GW observing run; even 17 neutron star mergers with only 50% coverage to a depth of -16 mag would constrain the maximum fraction of bright kilonovae to <25%.
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| 33. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 34. |
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| 35. |
- Gudbjartsson, Daniel F., et al.
(author)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
-
Journal article (peer-reviewed)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 36. |
- Van Doesum, Niels J., et al.
(author)
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Social mindfulness and prosociality vary across the globe
- 2021
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:35
-
Journal article (peer-reviewed)abstract
- Humans are social animals, but not everyone will be mindful of others to the same extent. Individual differences have been found, but would social mindfulness also be shaped by one's location in the world? Expecting cross-national differences to exist, we examined if and how social mindfulness differs across countries. At little to no material cost, social mindfulness typically entails small acts of attention or kindness. Even though fairly common, such low-cost cooperation has received little empirical attention. Measuring social mindfulness across 31 samples from industrialized countries and regions (n = 8,354), we found considerable variation. Among selected country-level variables, greater social mindfulness was most strongly associated with countries' better general performance on environmental protection. Together, our findings contribute to the literature on prosociality by targeting the kind of everyday cooperation that is more focused on communicating benevolence than on providing material benefits.
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| 37. |
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| 38. |
- Lebzelter, T., et al.
(author)
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Comparative modelling of the spectra of cool giants
- 2012
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 547, s. A108-
-
Journal article (peer-reviewed)abstract
- Context. Our ability to extract information from the spectra of stars depends on reliable models of stellar atmospheres and appropriate techniques for spectral synthesis. Various model codes and strategies for the analysis of stellar spectra are available today. Aims. We aim to compare the results of deriving stellar parameters using different atmosphere models and different analysis strategies. The focus is set on high-resolution spectroscopy of cool giant stars. Methods. Spectra representing four cool giant stars were made available to various groups and individuals working in the area of spectral synthesis, asking them to derive stellar parameters from the data provided. The results were discussed at a workshop in Vienna in 2010. Most of the major codes currently used in the astronomical community for analyses of stellar spectra were included in this experiment. Results. We present the results from the different groups, as well as an additional experiment comparing the synthetic spectra produced by various codes for a given set of stellar parameters. Similarities and differences of the results are discussed. Conclusions. Several valid approaches to analyze a given spectrum of a star result in quite a wide range of solutions. The main causes for the differences in parameters derived by different groups seem to lie in the physical input data and in the details of the analysis method. This clearly shows how far from a definitive abundance analysis we still are.
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| 39. |
- Steffen, Will, et al.
(author)
-
Stratigraphic and Earth System approaches to defining the Anthropocene
- 2016
-
In: Earth's Future. - 2328-4277. ; 4:8, s. 324-345
-
Research review (peer-reviewed)abstract
- Stratigraphy provides insights into the evolution and dynamics of the Earth System over its long history. With recent developments in Earth System science, changes in Earth System dynamics can now be observed directly and projected into the near future. An integration of the two approaches provides powerful insights into the nature and significance of contemporary changes to Earth. From both perspectives, the Earth has been pushed out of the Holocene Epoch by human activities, with the mid-20th century a strong candidate for the start date of the Anthropocene, the proposed new epoch in Earth history. Here we explore two contrasting scenarios for the future of the Anthropocene, recognizing that the Earth System has already undergone a substantial transition away from the Holocene state. A rapid shift of societies toward the UN Sustainable Development Goals could stabilize the Earth System in a state with more intense interglacial conditions than in the late Quaternary climate regime and with little further biospheric change. In contrast, a continuation of the present Anthropocene trajectory of growing human pressures will likely lead to biotic impoverishment and a much warmer climate with a significant loss of polar ice.
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| 40. |
- Purdum, Josiah N., et al.
(author)
-
Time-series and Phase-curve Photometry of the Episodically Active Asteroid (6478) Gault in a Quiescent State Using APO, GROWTH, P200, and ZTF
- 2021
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 911:2
-
Journal article (peer-reviewed)abstract
- We observed the episodically active asteroid (6478) Gault in 2020 with multiple telescopes in Asia and North America and found that it is no longer active after its recent outbursts at the end of 2018 and the start of 2019. The inactivity during this apparition allowed us to measure the absolute magnitude of Gault of H ( r ) = 14.63 +/- 0.02, G ( r ) = 0.21 +/- 0.02 from our secular phase-curve observations. In addition, we were able to constrain Gault's rotation period using time-series photometric lightcurves taken over 17 hr on multiple days in 2020 August, September, and October. The photometric lightcurves have a repeating less than or similar to 0.05 mag feature suggesting that (6478) Gault has a rotation period of similar to 2.5 hr and may have a semispherical or top-like shape, much like the near-Earth asteroids Ryugu and Bennu. The rotation period of similar to 2.5 hr is near the expected critical rotation period for an asteroid with the physical properties of (6478) Gault, suggesting that its activity observed over multiple epochs is due to surface mass shedding from its fast rotation spin-up by the Yarkovsky-O'Keefe-Radzievskii-Paddack effect.
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| 41. |
- Carvalho, M. R., et al.
(author)
-
Extinction at the end-Cretaceous and the origin of modern Neotropical rainforests
- 2021
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6537
-
Journal article (peer-reviewed)abstract
- The end-Cretaceous event was catastrophic for terrestrial communities worldwide, yet its long-lasting effect on tropical forests remains largely unknown. We quantified plant extinction and ecological change in tropical forests resulting from the end-Cretaceous event using fossil pollen (>50,000 occurrences) and leaves (>6000 specimens) from localities in Colombia. Late Cretaceous (Maastrichtian) rainforests were characterized by an open canopy and diverse plant-insect interactions. Plant diversity declined by 45% at the Cretaceous-Paleogene boundary and did not recover for similar to 6 million years. Paleocene forests resembled modern Neotropical rainforests, with a closed canopy and multistratal structure dominated by angiosperms. The end-Cretaceous event triggered a long interval of low plant diversity in the Neotropics and the evolutionary assembly of today's most diverse terrestrial ecosystem.
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| 42. |
- Jang, Kyung-Jin, et al.
(author)
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Reproducing human and cross-species drug toxicities using a Liver-Chip
- 2019
-
In: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 11:517
-
Journal article (peer-reviewed)abstract
- Nonclinical rodent and nonrodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans, contributing to drug failures in the clinic. Here, we applied microengineered Organs-on-Chips technology to design a rat, dog, and human Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chip detected diverse phenotypes of liver toxicity, including hepatocellular injury, steatosis, cholestasis, and fibrosis, and species-specific toxicities when treated with tool compounds. A multispecies Liver-Chip may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.
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| 43. |
- Pervjakova, Natalia, et al.
(author)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
-
Journal article (peer-reviewed)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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