| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 4. |
- Bombarda, F., et al.
(author)
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Runaway electron beam control
- 2019
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In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Journal article (peer-reviewed)
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| 5. |
- Krasilnikov, A., et al.
(author)
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Evidence of 9 Be + p nuclear reactions during 2ω CH and hydrogen minority ICRH in JET-ILW hydrogen and deuterium plasmas
- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
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Journal article (peer-reviewed)abstract
- The intensity of 9Be + p nuclear fusion reactions was experimentally studied during second harmonic (2ω CH) ion-cyclotron resonance heating (ICRH) and further analyzed during fundamental hydrogen minority ICRH of JET-ILW hydrogen and deuterium plasmas. In relatively low-density plasmas with a high ICRH power, a population of fast H+ ions was created and measured by neutral particle analyzers. Primary and secondary nuclear reaction products, due to 9Be + p interaction, were observed with fast ion loss detectors, γ-ray spectrometers and neutron flux monitors and spectrometers. The possibility of using 9Be(p, d)2α and 9Be(p, α)6Li nuclear reactions to create a population of fast alpha particles and study their behaviour in non-active stage of ITER operation is discussed in the paper.
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| 6. |
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- 2018
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Research review (peer-reviewed)
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Overview of the JET results
- 2015
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Journal article (peer-reviewed)
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| 29. |
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| 30. |
- Gould, Rebecca L., et al.
(author)
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Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND) : a multicentre, parallel, randomised controlled trial in the UK
- 2024
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 403:10442, s. 2381-2394
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Journal article (peer-reviewed)abstract
- Background: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease.Methods: We conducted a parallel, multicentre, two -arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory -supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web -based system, stratified by site. Participants were followed up at 6 months and 9 months post -randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire -Revised (MQOL-R) at 6 months post -randomisation. Primary analyses were multi -level modelling and modified intention to treat among participants with available data. This trial was pre -registered with the ISRCTN Registry (ISRCTN12655391).Findings: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63⋅1 years (SD 11⋅0). 155 (81%) participants had primary outcome data at 6 months post -randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0⋅66 [95% CI 0⋅22-1⋅10]; d=0⋅46 [0⋅16-0⋅77]; p=0⋅0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention.Interpretation: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services.
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| 38. |
- Christmas, Matthew, et al.
(author)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Journal article (peer-reviewed)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 39. |
- Meadows, J R S, et al.
(author)
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Haplogroup relationships between domestic and wild sheep resolved using a mitogenome panel
- 2011
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In: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 106:4, s. 700-706
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Journal article (peer-reviewed)abstract
- Five haplogroups have been identified in domestic sheep through global surveys of mitochondrial (mt) sequence variation, however these group classifications are often based on small fragments of the complete mtDNA sequence; partial control region or the cytochrome B gene. This study presents the complete mitogenome from representatives of each haplogroup identified in domestic sheep, plus a sample of their wild relatives. Comparison of the sequence successfully resolved the relationships between each haplogroup and provided insight into the relationship with wild sheep. The five haplogroups were characterised as branching independently, a radiation that shared a common ancestor 920,000 ± 190,000 years ago based on protein coding sequence. The utility of various mtDNA components to inform the true relationship between sheep was also examined with Bayesian, maximum likelihood and partitioned Bremmer support analyses. The control region was found to be the mtDNA component, which contributed the highest amount of support to the tree generated using the complete data set. This study provides the nucleus of a mtDNA mitogenome panel, which can be used to assess additional mitogenomes and serve as a reference set to evaluate small fragments of the mtDNA.
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| 42. |
- Susat, J., et al.
(author)
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A 5,000-year-old hunter-gatherer already plagued by Yersinia pestis
- 2021
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 35:13
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Journal article (peer-reviewed)abstract
- A 5,000-year-old Yersinia pestis genome (RV 2039) is reconstructed from a hunter-fisher-gatherer (5300-5050 cal BP) buried at RirmukaIns, Latvia. RV 2039 is the first in a series of ancient strains that evolved shortly after the split of Y. pestis from its antecessor Y. pseudotuberculosis similar to 7,000 years ago. The genomic and phylogenetic characteristics of RV 2039 are consistent with the hypothesis that this very early Y. pestis form was most likely less transmissible and maybe even less virulent than later strains. Our data do not support the scenario of a prehistoric pneumonic plague pandemic, as suggested previously for the Neolithic decline. The geographical and temporal distribution of the few prehistoric Y. pestis cases reported so far is more in agreement with single zoonotic events.
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| 43. |
- Dahlqvist, Johanna, 1979-, et al.
(author)
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Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA
- 2022
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In: Rheumatology. - Oxford, United Kingdom : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 61:8, s. 3461-3470
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Journal article (peer-reviewed)abstract
- Objective To identify and characterize genetic loci associated with the risk of developing ANCA-associated vasculitides (AAV). Methods Genetic association analyses were performed after Illumina sequencing of 1853 genes and subsequent replication with genotyping of selected single nucleotide polymorphisms in a total cohort of 1110 Scandinavian cases with granulomatosis with polyangiitis or microscopic polyangiitis, and 1589 controls. A novel AAV-associated single nucleotide polymorphism was analysed for allele-specific effects on gene expression using luciferase reporter assay. Results PR3-ANCA(+) AAV was significantly associated with two independent loci in the HLA-DPB1/HLA-DPA1 region [rs1042335, P = 6.3 x 10(-61), odds ratio (OR) 0.10; rs9277341, P = 1.5 x 10(-44), OR 0.22] and with rs28929474 in the SERPINA1 gene (P = 2.7 x 10(-10), OR 2.9). MPO-ANCA(+) AAV was significantly associated with the HLA-DQB1/HLA-DQA2 locus (rs9274619, P = 5.4 x 10(-25), OR 3.7) and with a rare variant in the BACH2 gene (rs78275221, P = 7.9 x 10(-7), OR 3.0), the latter a novel susceptibility locus for MPO-ANCA(+) granulomatosis with polyangiitis/microscopic polyangiitis. The rs78275221-A risk allele reduced luciferase gene expression in endothelial cells, specifically, as compared with the non-risk allele. Conclusion We identified a novel susceptibility locus for MPO-ANCA(+) AAV and propose that the associated variant is of mechanistic importance, exerting a regulatory function on gene expression in specific cell types.
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| 44. |
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| 45. |
- Fischer, Anders, 1951, et al.
(author)
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The Rodhals kitchen midden - marine adaptations at the end of the Mesolithic world
- 2021
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In: Journal of Archaeological Science-Reports. - : Elsevier BV. - 2352-409X. ; 39
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Journal article (peer-reviewed)abstract
- The Rodhals kitchen midden was located on a tiny stretch of land 18 km from the nearest major landmass in present-day Denmark. It dates to the Mesolithic-Neolithic transition, roughly 4300 to 3700 cal BC. Its inhabitants practiced a remarkably broad-scale exploitation of marine resources spanning from the collecting of mollusks on the sea-shore, over open-sea fowling and deep-water angling to the killing of small whales. The sparse traces of terrestrial diet are mainly from cattle, sheep, pig and cereals dating to a late stage of the habitation. Strategic raw materials of bone and antler from large forest game were only occasionally imported from across the sea. In terms of artefact types and production modes, the material culture of Rodhals represents the ultimate stage of the local fisher-hunter-gatherer Ertebolle Culture and an initial stage of the farming-based Funnel Beaker Culture. The extreme marine adaptation seen at this site may reflect a historically extraordinary situation, where an indigenous population of foragers had lost major parts of its territory to immigrant farmers.
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| 46. |
- Genereux, Diane P., et al.
(author)
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A comparative genomics multitool for scientific discovery and conservation
- 2020
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In: Nature. - : NATURE RESEARCH. - 0028-0836 .- 1476-4687. ; 587:7833, s. 240-245
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Journal article (peer-reviewed)abstract
- A whole-genome alignment of 240 phylogenetically diverse species of eutherian mammal-including 131 previously uncharacterized species-from the Zoonomia Project provides data that support biological discovery, medical research and conservation. The Zoonomia Project is investigating the genomics of shared and specialized traits in eutherian mammals. Here we provide genome assemblies for 131 species, of which all but 9 are previously uncharacterized, and describe a whole-genome alignment of 240 species of considerable phylogenetic diversity, comprising representatives from more than 80% of mammalian families. We find that regions of reduced genetic diversity are more abundant in species at a high risk of extinction, discern signals of evolutionary selection at high resolution and provide insights from individual reference genomes. By prioritizing phylogenetic diversity and making data available quickly and without restriction, the Zoonomia Project aims to support biological discovery, medical research and the conservation of biodiversity.
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| 47. |
- Gordon, David E., et al.
(author)
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Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
- 2020
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6521
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Journal article (peer-reviewed)abstract
- INTRODUCTIONThe emergence of three lethal coronaviruses in <20 years and the urgency of the COVID-19 pandemic have prompted efforts to develop new therapeutic strategies, including by repurposing existing agents. After performing a comparative analysis of the three pathogenic human coronaviruses severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV), we identified shared biology and host-directed drug targets to prioritize therapeutics with potential for rapid deployment against current and future coronavirus outbreaks.RATIONALEExpanding on our recent SARS-CoV-2 interactome, we mapped the virus-host protein-protein interactions for SARS-CoV-1 and MERS-CoV and assessed the cellular localization of each viral protein across the three strains. We conducted two genetic screens of SARS-CoV-2 interactors to prioritize functionally-relevant host factors and structurally characterized one virus-host interaction. We then tested the clinical relevance of three more host factors by assessing risk in genetic cohorts or observing effectiveness of host factor–targeting drugs in real-world evidence.RESULTSQuantitative comparison of the 389 interactors of SARS-CoV-2, 366 of SARS-CoV-1, and 296 of MERS-CoV highlighted interactions with host processes that are conserved across all three viruses, including where nonorthologous proteins from different virus strains seem to fill similar roles. We also localized each individually-expressed viral protein by microscopy and then raised and validated antisera against 14 SARS-CoV-2 proteins to determine their localization during infection.On the basis of two independent genetic perturbation screens, we identified 73 host factors that, when depleted, caused significant changes in SARS-CoV-2 replication. From this list of potential drug targets, we validated the biological and clinical relevance of Tom70, IL17RA, PGES-2, and SigmaR1.A 3-Å cryo–electron microscopy structure of Tom70, a mitochondrial import receptor, in complex with SARS-CoV-2 ORF9b, provides insight into how ORF9b may modulate the host immune response. Using curated genome-wide association study data, we found that individuals with genotypes corresponding to higher soluble IL17RA levels in plasma are at decreased risk of COVID-19 hospitalization.To demonstrate the value of our data for drug repurposing, we identified SARS-CoV-2 patients who were prescribed drugs against prioritized targets and asked how they fared compared with carefully matched patients treated with clinically similar drugs that do not inhibit SARS-CoV-2. Both indomethacin, an inhibitor of host factor PGES-2, and typical antipsychotics, selected for their interaction with sigma receptors, showed effectiveness against COVID-19 compared with celecoxib and atypical antipsychotics, respectively.CONCLUSIONBy employing an integrative and collaborative approach, we identified conserved mechanisms across three pathogenic coronavirus strains and further investigated potential drug targets. This versatile approach is broadly applicable to other infectious agents and disease areas.
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| 48. |
- Höppner, Marc P., et al.
(author)
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An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes and Non-Coding Transcripts
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e91172-
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Journal article (peer-reviewed)abstract
- The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog similar to 175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional similar to 3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to,20,700 high-confidence protein coding loci, we found,4,600 antisense transcripts overlapping exons of protein coding genes, similar to 7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and,11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.
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| 49. |
- Kitko, Lisa, et al.
(author)
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Family Caregiving for Individuals With Heart Failure: A Scientific Statement From the American Heart Association
- 2020
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 141:22, s. E864-E878
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Journal article (peer-reviewed)abstract
- Many individuals living with heart failure (HF) rely on unpaid support from their partners, family members, friends, or neighbors as caregivers to help manage their chronic disease. Given the advancements in treatments and devices for patients with HF, caregiving responsibilities have expanded in recent decades to include more intensive care for increasingly precarious patients with HF-tasks that would previously have been undertaken by healthcare professionals in clinical settings. The specific tasks of caregivers of patients with HF vary widely based on the patients symptoms and comorbidities, the relationship between patient and caregiver, and the complexity of the treatment regimen. Effects of caregiving on the caregiver and patient range from physical and psychological to financial. Therefore, it is critically important to understand the needs of caregivers to support the increasingly complex medical care they provide to patients living with HF. This scientific statement synthesizes the evidence pertaining to caregiving of adult individuals with HF in order to (1) characterize the HF caregiving role and how it changes with illness trajectory; (2) describe the financial, health, and well-being implications of caregiving in HF; (3) evaluate HF caregiving interventions to support caregiver and patient outcomes; (4) summarize existing policies and resources that support HF caregivers; and (5) identify knowledge gaps and future directions for providers, investigators, health systems, and policymakers.
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| 50. |
- Lundtoft, Christian, et al.
(author)
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The HLA region in ANCA-associated vasculitis : characterisation of genetic associations in a Scandinavian patient population
- 2024
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In: RMD Open. - : BMJ PUBLISHING GROUP. - 2056-5933. ; 10:2, s. 1-10
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are inflammatory disorders with ANCA autoantibodies recognising either proteinase 3 (PR3-AAV) or myeloperoxidase (MPO-AAV). PR3-AAV and MPO-AAV have been associated with distinct loci in the human leucocyte antigen (HLA) region. While the association between MPO-AAV and HLA has been well characterised in East Asian populations where MPO-AAV is more common, studies in populations of European descent are limited. The aim of this study was to thoroughly characterise associations to the HLA region in Scandinavian patients with PR3-AAV as well as MPO-AAV.METHODS: Genotypes of single-nucleotide polymorphisms (SNPs) located in the HLA region were extracted from a targeted exome-sequencing dataset comprising Scandinavian AAV cases and controls. Classical HLA alleles were called using xHLA. After quality control, association analyses were performed of a joint SNP/classical HLA allele dataset for cases with PR3-AAV (n=411) and MPO-AAV (n=162) versus controls (n=1595). Disease-associated genetic variants were analysed for association with organ involvement, age at diagnosis and relapse, respectively.RESULTS: PR3-AAV was significantly associated with both HLA-DPB1*04:01 and rs1042335 at the HLA-DPB1 locus, also after stepwise conditional analysis. MPO-AAV was significantly associated with HLA-DRB1*04:04. Neither carriage of HLA-DPB1*04:01 alleles in PR3-AAV nor of HLA-DRB1*04:04 alleles in MPO-AAV were associated with organ involvement, age at diagnosis or relapse. CONCLUSIONS: The association to the HLA region was distinct in Scandinavian cases with MPO-AAV compared with cases of East Asian descent. In PR3-AAV, the two separate signals of association to the HLD-DPB1 region mediate potentially different functional effects.
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