| 1. |
- Groth, Sanne Krogh, et al.
(författare)
-
Sound Art : The First 100 Years of an Aggressively Expanding Artform
- 2020
-
Ingår i: The Bloomsbury Handbook of Sound Art. - 9781501338793 - 9781501338816 ; , s. 1-20
-
Bokkapitel (refereegranskat)abstract
- "A brief history of sound art is, in a nutshell, a history of sonic forms of expression that throughout the twentieth century can be traced within music, the visual arts, and contemporary dance, as well as in performance art, conceptual art, and media art. Attempts to capture sound art as a detached and isolated art form or artistic phenomenon have been made, but this is definitely not the approach of this handbook. On the contrary, we conceptualize sound art as a persistent and expanding art form, that is entangled with a broad diversity of genres and cultural phenomena—through its sound practices. Sound art today both stimulates and builds, challenges and destructs, reinvents and subverts institutions. It is concrete and physical, material and corporeal—calling for reflection, speculation, and abstraction to surprisingly excessive degrees. Sound art is rooted in a longer history and culture, but incessantly seeks a critical politicizing, decolonializing, and rethinking of the same. A history of sound art can, of course, be shaped in various ways depending on the argument or approach one wishes to frame. In order to support our argument we stress a canon of works and approaches that consider technology, performativity, social and political awareness, and utopia and dystopia. These are, in our understanding the main reasons why today it still holds true to claim: Sound art is generative....With this handbook we hope ... to provide a contemporary journey in postapocalyptic times across the grid of sensibilities, thinking, making, and institutionalizing that can serve artists, curators, activists, developers, inventors, listeners, researchers, and aficionados as well. May sound art further expand!"
|
|
| 2. |
- Valassi, Andrea, et al.
(författare)
-
Challenges in Monte Carlo Event Generator Software for High-Luminosity LHC
- 2021
-
Ingår i: Computing and Software for Big Science. - : Springer Science and Business Media LLC. - 2510-2044 .- 2510-2036. ; 5:1
-
Tidskriftsartikel (refereegranskat)abstract
- We review the main software and computing challenges for the Monte Carlo physics event generators used by the LHC experiments, in view of the High-Luminosity LHC (HL-LHC) physics programme. This paper has been prepared by the HEP Software Foundation (HSF) Physics Event Generator Working Group as an input to the LHCC review of HL-LHC computing, which has started in May 2020.
|
|
| 3. |
- Wiedorn, Max O., et al.
(författare)
-
Megahertz serial crystallography
- 2018
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
|
|
| 4. |
- Albrecht, Eva, et al.
(författare)
-
Telomere length in circulating leukocytes is associated with lung function and disease
- 2014
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 43:4, s. 983-992
-
Tidskriftsartikel (refereegranskat)abstract
- Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
|
|
| 5. |
- Anchordoqui, Luis A., et al.
(författare)
-
The Forward Physics Facility : Sites, experiments, and physics potential
- 2022
-
Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 968, s. 1-50
-
Tidskriftsartikel (refereegranskat)abstract
- The Forward Physics Facility (FPF) is a proposal to create a cavern with the space and infrastructure to support a suite of far-forward experiments at the Large Hadron Collider during the High Luminosity era. Located along the beam collision axis and shielded from the interaction point by at least 100 m of concrete and rock, the FPF will house experiments that will detect particles outside the acceptance of the existing large LHC experiments and will observe rare and exotic processes in an extremely low-background environment. In this work, we summarize the current status of plans for the FPF, including recent progress in civil engineering in identifying promising sites for the FPF and the experiments currently envisioned to realize the FPF's physics potential. We then review the many Standard Model and new physics topics that will be advanced by the FPF, including searches for long-lived particles, probes of dark matter and dark sectors, high-statistics studies of TeV neutrinos of all three flavors, aspects of perturbative and non-perturbative QCD, and high-energy astroparticle physics.
|
|
| 6. |
- Aquila, Andrew, et al.
(författare)
-
Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
-
Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
|
|
| 7. |
- Artigas Soler, María, et al.
(författare)
-
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
-
Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
|
|
| 8. |
- Aschard, Hugues, et al.
(författare)
-
Evidence for large-scale gene-by-smoking interaction effects on pulmonary function
- 2017
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:3, s. 894-904
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking.METHODS: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia.RESULTS: We identified an interaction (βint = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV 1: /FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect.CONCLUSIONS: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
|
|
| 9. |
- Ayyer, Kartik, et al.
(författare)
-
3D diffractive imaging of nanoparticle ensembles using an x-ray laser
- 2021
-
Ingår i: Optica. - : Optical Society of America. - 2334-2536. ; 8:1, s. 15-23
-
Tidskriftsartikel (refereegranskat)abstract
- Single particle imaging at x-ray free electron lasers (XFELs) has the potential to determine the structure and dynamics of single biomolecules at room temperature. Two major hurdles have prevented this potential from being reached, namely, the collection of sufficient high-quality diffraction patterns and robust computational purification to overcome structural heterogeneity. We report the breaking of both of these barriers using gold nanoparticle test samples, recording around 10 million diffraction patterns at the European XFEL and structurally and orientationally sorting the patterns to obtain better than 3-nm-resolution 3D reconstructions for each of four samples. With these new developments, integrating advancements in x-ray sources, fast-framing detectors, efficient sample delivery, and data analysis algorithms, we illuminate the path towards sub-nano meter biomolecular imaging. The methods developed here can also be extended to characterize ensembles that are inherently diverse to obtain their full structural landscape. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.
|
|
| 10. |
- Bierlich, Christian, et al.
(författare)
-
Robust independent validation of experiment and theory : RIVET version 3
- 2020
-
Ingår i: SciPost Physics. - 2542-4653. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- First released in 2010, the RIVET library forms an important repository for analysis code, facilitating comparisons between measurements of the final state in particle collisions and theoretical calculations of those final states. We give an overview of RIVET’s current design and implementation, its uptake for analysis preservation and physics results, and summarise recent developments including propagation of MC systematic-uncertainty weights, heavy-ion and ep physics, and systems for detector emulation. In addition, we provide a short user guide that supplements and updates the RIVET user manual.
|
|
| 11. |
- Buckley, Andy, et al.
(författare)
-
Rivet user manual
- 2013
-
Ingår i: Computer Physics Communications. - : Elsevier BV. - 0010-4655. ; 184:12, s. 2803-2819
-
Tidskriftsartikel (refereegranskat)abstract
- This is the manual and user guide for the Rivet system for the validation and tuning of Monte Carlo event generators. As well as the core Rivet library, this manual describes the usage of the rivet program and the AGILe generator interface library. The depth and level of description is chosen for users of the system, starting with the basics of using validation code written by others, and then covering sufficient details to write new Rivet analyses and calculational components. Program summary Program title: Rivet Catalogue identifier: AEPS_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEPS_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 571126 No. of bytes in distributed program, including test data, etc.: 4717522 Distribution format: tar.gz Programming language: C++, Python. Computer: PC running Linux, Mac. Operating system: Linux, Mac OS. RAM: 20 MB Classification: 11.9, 11.2. External routines: HepMC (https://savannah.cern.ch/projects/hepmc/), GSL (http://www.gnu.org/software/gsl/manual/gsl-ref.html), FastJet (http://fastjet.fr/), Python (http://www.python.org/), Swig (http://www.swig.org/), Boost (http://www.boostsoftware.com/), YAML (http://www.yaml.org/spec/1.2/spec.html) Nature of problem: Experimental measurements from high-energy particle colliders should be defined and stored in a general framework such that it is simple to compare theory predictions to them. Rivet is such a framework, and contains at the same time a large collection of existing measurements. Solution method: Rivet is based on HepMC events, a standardised output format provided by many theory simulation tools. Events are processed by Rivet to generate histograms for the requested list of analyses, incorporating all experimental phase space cuts and histogram definitions. Restrictions: Cannot calculate statistical errors for correlated events as they appear in NLO calculations. Unusual features: It is possible for the user to implement and use their own custom analysis as a module without having to modify the main Rivet code/installation. Running time: Depends on the number and complexity of analyses being applied, but typically a few hundred events per second. (C) 2013 Elsevier B.V. All rights reserved.
|
|
| 12. |
- Buckley, Andy, et al.
(författare)
-
Systematic event generator tuning for the LHC
- 2010
-
Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 65:1-2, s. 331-357
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedIn this article we describe Professor, a new program for tuning model parameters of Monte Carlo event generators to experimental data by parameterising the per-bin generator response to parameter variations and numerically optimising the parameterised behaviour. Simulated experimental analysis data is obtained using the Rivet analysis toolkit. This paper presents the Professor procedure and implementation, illustrated with the application of the method to tunes of the Pythia 6 event generator to data from the LEP/SLD and Tevatron experiments. These tunes are substantial improvements on existing standard choices, and are recommended as base tunes for LHC experiments, to be themselves systematically improved upon when early LHC data is available.
|
|
| 13. |
- Bustamante, Mariona, et al.
(författare)
-
A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways.
- 2016
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:18, s. 4127-4142
-
Tidskriftsartikel (refereegranskat)abstract
- More than a million childhood diarrhoeal episodes occur worldwide each year, and in developed countries a considerable part of them are caused by viral infections. In this study, we aimed to search for genetic variants associated with diarrhoeal disease in young children by meta-analyzing genome-wide association studies, and to elucidate plausible biological mechanisms. The study was conducted in the context of the Early Genetics and Lifecourse Epidemiology (EAGLE) consortium. Data about diarrhoeal disease in two time windows (around 1 year of age and around 2 years of age) was obtained via parental questionnaires, doctor interviews or medical records. Standard quality control and statistical tests were applied to the 1000 Genomes imputed genotypic data. The meta-analysis (N=5758) followed by replication (N=3784) identified a genome-wide significant association between rs8111874 and diarrhoea at age 1 year. Conditional analysis suggested that the causal variant could be rs601338 (W154X) in the FUT2 gene. Children with the A allele, which results in a truncated FUT2 protein, had lower risk of diarrhoea. FUT2 participates in the production of histo-blood group antigens and has previously been implicated in the susceptibility to infections, including Rotavirus and Norovirus Gene-set enrichment analysis suggested pathways related to the histo-blood group antigen production, and the regulation of ion transport and blood pressure. Among others, the gastrointestinal tract, and the immune and neuro-secretory systems were detected as relevant organs. In summary, this genome-wide association meta-analysis suggests the implication of the FUT2 gene in diarrhoeal disease in young children from the general population.
|
|
| 14. |
- Delgado, Luis Fernando, et al.
(författare)
-
Phylogeny-based comparative genomics of Vibrio vulnificus links genetic traits to pathogenicity
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Vibrio vulnificus is a natural part of the microbiome of brackish waters worldwide. It is also an opportunistic pathogen that can cause severe infections and septicemia via consumption of seafood or through wound infections. The species possess diverse virulence factors, yet its precise disease mechanism remains undefined. Comparative genomics between clinical and environmental isolates offers a means to identify key virulence genes, but the scarcity of environmental isolates for V. vulnificus has constituted a significant limitation. Here we sequenced genomes of 82 V. vulnificus isolates from water, sediment and seagrass surface from stations along the Baltic Sea coast and complemented these with 208 and 117 previously sequenced clinical and environmental genomes, respectively, in a comparative analysis. Phylogenetic reconstruction corroborated earlier analysis with four main lineages forming within the species. Strains from the Baltic Sea region were confined to certain phylogenetic lineages (L4 and sublineages L2c and L2e) whereas clinical and environmental strains were found in all lineages, indicting that the phylogenetic structure of V. vulnificus reflects adaptations to specific environmental conditions rather than pathogenicity. Employing orthologue enrichment analysis in a phylogenetic framework using the PhyloBOTL pipeline developed in this work revealed 58 significantly enriched orthologs in clinical compared to environmental isolates. These orthologs were grouped into 18 co-localisation clusters based on the corresponding genes’ proximity in the genomes. The co-localisation clusters entailed clusters with 1 genes previously linked with pathogenicity in V. vulnificus, such as genes for capsular polysaccharide (CPS) synthesis and biofilm formation, but also clusters with genes not previously associated with virulence in the species. Examples of the latter were genes for pilus biosynthesis of the usher-chaperone (CU) pathway, for spermidine synthesis, and for effector proteins of the Type VI secretion system. Finally we leveraged on the clinically enriched genes to design PCR primers for detection and surveillance of pathogenic V. vulnificus strains.
|
|
| 15. |
- Ekeberg, Tomas, 1983-, et al.
(författare)
-
Three-dimensional structure determination with an X-ray laser
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Three-dimensional structure determination of a non-crystalline virus has been achieved from a set of randomly oriented continuous diffraction patterns captured with an X-ray laser. Intense, ultra-short X-ray pulses intercepted a beam of single mimivirus particles, producing single particle X-ray diffraction patterns that are assembled into a three-dimensional amplitude distribution based on statistical consistency. Phases are directly retrieved from the assembled Fourier distribution to synthesize a three-dimensional image. The resulting electron density reveals a pseudo-icosahedral asymmetric virion structure with a compartmentalized interior, within which the DNA genome occupies only about a fifth of the volume enclosed by the capsid. Additional electron microscopy data indicate the genome has a chromatin-like fiber structure that has not previously been observed in a virus.
|
|
| 16. |
- Fieg, Max, et al.
(författare)
-
Tuning pythia for forward physics experiments
- 2024
-
Ingår i: Physical Review D. - 2470-0010. ; 109:1
-
Tidskriftsartikel (refereegranskat)abstract
- Event generators like pythia play an important role in physics studies at the Large Hadron Collider (LHC). While they make accurate predictions in the central region, i.e., at pseudorapidities η<5, a disagreement between pythia and measurements in the forward region η>7 has been observed. We introduce a dedicated forward physics tune for the pythia event generator to be used for forward physics studies at the LHC, which uses a more flexible modeling of beam remnant hadronization and is tuned to available particle spectra measured by LHCf. Furthermore, we provide an uncertainty estimate on the new tune in a data-driven way which can be used as a means of flux uncertainty for future forward physics studies. We demonstrate an application of our tune by showing the updated neutrino and dark photon spectra at the FASER experiment.
|
|
| 17. |
- Flexeder, Claudia, et al.
(författare)
-
Second-hand smoke exposure in adulthood and lower respiratory health during 20 year follow up in the European Community Respiratory Health Survey
- 2019
-
Ingår i: Respiratory Research. - : BioMed Central. - 1465-9921 .- 1465-993X. ; 20
-
Tidskriftsartikel (refereegranskat)abstract
- Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (beta: - 49 ml; 95%-CI: -132, 35 for FEV1 and beta: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes.
|
|
| 18. |
- Höche, Stefan, et al.
(författare)
-
Simulation of vector boson plus many jet final states at the high luminosity LHC
- 2019
-
Ingår i: Physical Review D. - 2470-0010. ; 100:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present a novel event-generation framework for the efficient simulation of vector boson plus multijet backgrounds at the high-luminosity LHC and at possible future hadron colliders. Message passing interface parallelization of parton-level and particle-level event generation and storage of parton-level event information using the HDF5 data format allow us to obtain leading-order merged Monte Carlo predictions with up to nine jets in the final state. The parton-level event samples generated in this manner correspond to an integrated luminosity of 3 ab-1 and are made publicly available for future phenomenological studies.
|
|
| 19. |
- Imboden, Medea, et al.
(författare)
-
Epigenome-wide association study of lung function level and its change
- 2019
-
Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:1
-
Tidskriftsartikel (refereegranskat)abstract
- Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
|
|
| 20. |
- Jackson, Victoria E, et al.
(författare)
-
Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
-
Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
|
|
| 21. |
- Johansson, Linda C, 1983, et al.
(författare)
-
Lipidic phase membrane protein serial femtosecond crystallography.
- 2012
-
Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 9:3, s. 263-265
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.
|
|
| 22. |
- Kassemeyer, Stephan, et al.
(författare)
-
Femtosecond free-electron laser x-ray diffraction data sets for algorithm development
- 2012
-
Ingår i: Optics Express. - 1094-4087. ; 20:4, s. 4149-4158
-
Tidskriftsartikel (refereegranskat)abstract
- We describe femtosecond X-ray diffraction data sets of viruses and nanoparticles collected at the Linac Coherent Light Source. The data establish the first large benchmark data sets for coherent diffraction methods freely available to the public, to bolster the development of algorithms that are essential for developing this novel approach as a useful imaging technique. Applications are 2D reconstructions, orientation classification and finally 3D imaging by assembling 2D patterns into a 3D diffraction volume.
|
|
| 23. |
- Koopmann, Rudolf, et al.
(författare)
-
In vivo protein crystallization opens new routes in structural biology
- 2012
-
Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 9:3, s. 259-262
-
Tidskriftsartikel (refereegranskat)abstract
- Protein crystallization in cells has been observed several times in nature. However, owing to their small size these crystals have not yet been used for X-ray crystallographic analysis. We prepared nano-sized in vivo–grown crystals of Trypanosoma brucei enzymes and applied the emerging method of free-electron laser-based serial femtosecond crystallography to record interpretable diffraction data. This combined approach will open new opportunities in structural systems biology.
|
|
| 24. |
- Loh, N. Duane, et al.
(författare)
-
Sensing the wavefront of x-ray free-electron lasers using aerosol spheres
- 2013
-
Ingår i: Optics Express. - 1094-4087. ; 21:10, s. 12385-12394
-
Tidskriftsartikel (refereegranskat)abstract
- Characterizing intense, focused x-ray free electron laser (FEL) pulses is crucial for their use in diffractive imaging. We describe how the distribution of average phase tilts and intensities on hard x-ray pulses with peak intensities of 1021 W/m(2) can be retrieved from an ensemble of diffraction patterns produced by 70 nm-radius polystyrene spheres, in a manner that mimics wavefront sensors. Besides showing that an adaptive geometric correction may be necessary for diffraction data from randomly injected sample sources, our paper demonstrates the possibility of collecting statistics on structured pulses using only the diffraction patterns they generate and highlights the imperative to study its impact on single-particle diffractive imaging.
|
|
| 25. |
- Lomb, Lukas, et al.
(författare)
-
Radiation damage in protein serial femtosecond crystallography using an x-ray free-electron laser
- 2011
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 84:21, s. 214111-1-214111-6
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron lasers deliver intense femtosecond pulses that promise to yield high resolution diffraction data of nanocrystals before the destruction of the sample by radiation damage. Diffraction intensities of lysozyme nanocrystals collected at the Linac Coherent Light Source using 2 keV photons were used for structure determination by molecular replacement and analyzed for radiation damage as a function of pulse length and fluence. Signatures of radiation damage are observed for pulses as short as 70 fs. Parametric scaling used in conventional crystallography does not account for the observed effects.
|
|
