| 1. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 2. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 3. |
- Nagaya, K., et al.
(författare)
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Unusual under-threshold ionization of neon clusters studied by ion spectroscopy
- 2013
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Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 46:16 SI
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Tidskriftsartikel (refereegranskat)abstract
- We carried out time-of-flight mass spectrometry for neon clusters that were exposed to intense free electron laser pulses with the wavelength of 62 nm, which induce optical transition from the ground state (2s(2) 2p(6)) to an excited state (2s(2) 2p(5) nl) in the Ne atoms. In contrast to Ne+ ions produced by two-photon absorption from isolated Ne atoms, the Ne+ ion yield from Ne clusters shows a linear dependence on the laser intensity (I). We discuss the ionization mechanisms which give the linear behaviour with respect to I and expected features in the electron emission spectrum.
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| 4. |
- Sugishima, A., et al.
(författare)
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Charge and energy transfer in argon-core-neon-shell clusters irradiated by free-electron-laser pulses at 62 nm
- 2012
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 86:3, s. 033203-
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Tidskriftsartikel (refereegranskat)abstract
- The multiple ionization of Ar-core-Ne-shell clusters in intense extreme-ultraviolet laser pulses (lambda similar to 62 nm) from the free-electron laser in Japan was investigated utilizing a momentum imaging technique. The Ar composition dependence of the kinetic energies and the yields of the fragment ions give evidence for charge transfer from the Ar core to the Ne shell. We have extended the uniformly charged sphere model originally applied to pristine clusters [Islam et al., Phys. Rev. A 73, 041201 (R) (2006)] to the core-shell heterogeneous clusters to estimate the amounts of charge and energy transfers.
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| 5. |
- Yamada, A., et al.
(författare)
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Ion-ion coincidence studies on multiple ionizations of N-2 and O-2 molecules irradiated by extreme ultraviolet free-electron laser pulses
- 2010
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 132:20, s. 204305-
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated multiple ionization of N-2 and O-2 molecules by 52 nm extreme-ultraviolet light pulses at the free-electron laser facility SCSS in Japan. Coulomb break-up of parent ions with charge states up to 5+ is found by the ion-ion coincidence technique. The charge-state dependence of kinetic energy release distributions suggests that the electrons are emitted sequentially in competition with the elongation of the bond length.
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| 6. |
- Moshammer, R., et al.
(författare)
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Few-photon multiple ionization of Ne and Ar by strong free-electron-laser pulses
- 2007
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:20, s. 203001-
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Tidskriftsartikel (refereegranskat)abstract
- Few-photon multiple ionization of Ne and Ar atoms by strong vacuum ultraviolet laser pulses from the free-electron laser at Hamburg was investigated differentially with the Heidelberg reaction microscope. The light-intensity dependence of Ne2+ production reveals the dominance of nonsequential two-photon double ionization at intensities of I < 6x10(12) W/cm(2) and significant contributions of three-photon ionization as I increases. Ne2+ recoil-ion-momentum distributions suggest that two electrons absorbing "instantaneously" two photons are ejected most likely into opposite hemispheres with similar energies.
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| 7. |
- Dupont, A., et al.
(författare)
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Age-Dependent Susceptibility to Enteropathogenic Escherichia coli (EPEC) Infection in Mice
- 2016
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Ingår i: Plos Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Enteropathogenic Escherichia coli (EPEC) represents a major causative agent of infant diarrhea associated with significant morbidity and mortality in developing countries. Although studied extensively in vitro, the investigation of the host-pathogen interaction in vivo has been hampered by the lack of a suitable small animal model. Using RT-PCR and global transcriptome analysis, high throughput 16S rDNA sequencing as well as immunofluorescence and electron microscopy, we characterize the EPEC-host interaction following oral challenge of newborn mice. Spontaneous colonization of the small intestine and colon of neonate mice that lasted until weaning was observed. Intimate attachment to the epithelial plasma membrane and microcolony formation were visualized only in the presence of a functional bundle forming pili (BFP) and type III secretion system (T3SS). Similarly, a T3SS-dependent EPEC-induced innate immune response, mediated via MyD88, TLR5 and TLR9 led to the induction of a distinct set of genes in infected intestinal epithelial cells. Infection-induced alterations of the microbiota composition remained restricted to the postnatal period. Although EPEC colonized the adult intestine in the absence of a competing microbiota, no microcolonies were observed at the small intestinal epithelium. Here, we introduce the first suitable mouse infection model and describe an age-dependent, virulence factor-dependent attachment of EPEC to enterocytes in vivo.
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| 8. |
- Rolles, D., et al.
(författare)
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Femtosecond x-ray photoelectron diffraction on gas-phase dibromobenzene molecules
- 2014
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 47:12
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Tidskriftsartikel (refereegranskat)abstract
- We present time-resolved femtosecond photoelectron momentum images and angular distributions of dissociating, laser-aligned 1,4-dibromobenzene (C6H4Br2) molecules measured in a near-infrared pump, soft-x-ray probe experiment performed at an x-ray free-electron laser. The observed alignment dependence of the bromine 2p photoelectron angular distributions is compared to density functional theory calculations and interpreted in terms of photoelectron diffraction. While no clear time-dependent effects are observed in the angular distribution of the Br(2p) photoelectrons, other, low-energy electrons show a pronounced dependence on the time delay between the near-infrared laser and the x-ray pulse.
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| 9. |
- Stern, S., et al.
(författare)
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Toward atomic resolution diffractive imaging of isolated molecules with X-ray free-electron lasers
- 2014
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Ingår i: Faraday Discussions. - : Royal Society of Chemistry (RSC). - 1364-5498. ; 171, s. 393-418
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Tidskriftsartikel (refereegranskat)abstract
- We give a detailed account of the theoretical analysis and the experimental results of an X-ray-diffraction experiment on quantum-state selected and strongly laser-aligned gasphase ensembles of the prototypical large asymmetric rotor molecule 2,5-diiodobenzonitrile, performed at the Linac Coherent Light Source [Phys. Rev. Lett. 112, 083002 (2014)]. This experiment is the first step toward coherent diffractive imaging of structures and structural dynamics of isolated molecules at atomic resolution, i.e., picometers and femtoseconds, using X-ray free-electron lasers.
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