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- Ferreira, MA, et al.
(författare)
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Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1741-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
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| 4. |
- Gray, A. X., et al.
(författare)
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Ultrafast terahertz field control of electronic and structural interactions in vanadium dioxide
- 2018
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 98:4
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Tidskriftsartikel (refereegranskat)abstract
- Vanadium dioxide (VO2), an archetypal correlated-electron material, undergoes an insulator-metal transition near room temperature that exhibits electron-correlation-driven and structurally driven physics. Using ultrafast temperature- and fluence-dependent optical spectroscopy and x-ray scattering, we show that multiple interrelated electronic and structural processes in the nonequilibrium dynamics in VO2 can be disentangled in the time domain. Specifically, following intense subpicosecond terahertz (THz) electric-field excitation, a partial collapse of the insulating gap occurs within the first picosecond. At temperatures sufficiently close to the transition temperature and for THz peak fields above a threshold of approximately 1 MV/cm, this electronic reconfiguration initiates a change in lattice symmetry taking place on a slower timescale. We identify the kinetic energy increase of electrons tunneling in the strong electric field as the driving force, illustrating a promising method to control electronic and structural interactions in correlated materials on an ultrafast timescale.
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| 5. |
- Fuller, Franklin D, et al.
(författare)
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Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers
- 2017
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Ingår i: Nature Methods. - : Macmillan Publishers Ltd.. - 1548-7091 .- 1548-7105. ; 14, s. 443-449
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Tidskriftsartikel (refereegranskat)abstract
- X-ray crystallography at X-ray free-electron laser sources is a powerful method for studying macromolecules at biologically relevant temperatures. Moreover, when combined with complementary techniques like X-ray emission spectroscopy, both global structures and chemical properties of metalloenzymes can be obtained concurrently, providing insights into the interplay between the protein structure and dynamics and the chemistry at an active site. The implementation of such a multimodal approach can be compromised by conflicting requirements to optimize each individual method. In particular, the method used for sample delivery greatly affects the data quality. We present here a robust way of delivering controlled sample amounts on demand using acoustic droplet ejection coupled with a conveyor belt drive that is optimized for crystallography and spectroscopy measurements of photochemical and chemical reactions over a wide range of time scales. Studies with photosystem II, the phytochrome photoreceptor, and ribonucleotide reductase R2 illustrate the power and versatility of this method.
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| 6. |
- Wright, G. S., et al.
(författare)
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The Mid-Infrared Instrument for the James Webb Space Telescope, II: Design and Build
- 2015
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 127:953, s. 595-611
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Tidskriftsartikel (refereegranskat)abstract
- The Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST) provides measurements over the wavelength range 5 to 28: 5 mu m. MIRI has, within a single "package," four key scientific functions: photometric imaging, coronagraphy, single-source low-spectral resolving power (R similar to 100) spectroscopy, and medium-resolving power (R similar to 1500 to 3500) integral field spectroscopy. An associated cooler system maintains MIRI at its operating temperature of
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| 9. |
- Keable, Stephen M., et al.
(författare)
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Room temperature XFEL crystallography reveals asymmetry in the vicinity of the two phylloquinones in photosystem I
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Photosystem I (PS I) has a symmetric structure with two highly similar branches of pigments at the center that are involved in electron transfer, but shows very different efficiency along the two branches. We have determined the structure of cyanobacterial PS I at room temperature (RT) using femtosecond X-ray pulses from an X-ray free electron laser (XFEL) that shows a clear expansion of the entire protein complex in the direction of the membrane plane, when compared to previous cryogenic structures. This trend was observed by complementary datasets taken at multiple XFEL beamlines. In the RT structure of PS I, we also observe conformational differences between the two branches in the reaction center around the secondary electron acceptors A1A and A1B. The π-stacked Phe residues are rotated with a more parallel orientation in the A-branch and an almost perpendicular confirmation in the B-branch, and the symmetry breaking PsaB-Trp673 is tilted and further away from A1A. These changes increase the asymmetry between the branches and may provide insights into the preferential directionality of electron transfer.
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| 10. |
- Trigo, M., et al.
(författare)
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Fourier-transform inelastic X-ray scattering from time- and momentum-dependent phonon-phonon correlations
- 2013
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Ingår i: Nature Physics. - 1745-2473. ; 9:12, s. 790-794
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Tidskriftsartikel (refereegranskat)abstract
- The macroscopic characteristics of a material are determined by its elementary excitations, which dictate the response of the system to external stimuli. The spectrum of excitations is related to fluctuations in the density-density correlations and is typically measured through frequency-domain neutron(1) or X-ray(2-4) scattering. Time-domain measurements of these correlations could yield a more direct way to investigate the excitations of solids and their couplings both near to and far from equilibrium. Here we show that we can access large portions of the phonon dispersion of germanium by measuring the diffuse scattering from femtosecond X-ray free-electron laser pulses. A femtosecond optical laser pulse slightly quenches the vibrational frequencies, producing pairs of high-wavevector phonons with opposite momenta. These phonons manifest themselves as time-dependent coherences in the displacement correlations(5) probed by the X-ray scattering. As the coherences are preferentially created in regions of strong electron-phonon coupling, the time-resolved approach is a natural spectroscopic tool for probing low-energy collective excitations in solids, and their microscopic interactions.
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