| 1. |
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Adare, A., et al.
(författare)
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Measurement of High-p(T) single electrons from heavy-flavor decays in p+p collisions at root s=200 GeV
- 2006
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Ingår i: Physical Review Letters. - 1079-7114. ; 97:25
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Tidskriftsartikel (refereegranskat)abstract
- The momentum distribution of electrons from decays of heavy flavor (charm and bottom) for midrapidity |y|< 0.35 in p+p collisions at s=200 GeV has been measured by the PHENIX experiment at the BNL Relativistic Heavy Ion Collider over the transverse momentum range 0.3 < p(T)< 9 GeV/c. Two independent methods have been used to determine the heavy-flavor yields, and the results are in good agreement with each other. A fixed-order-plus-next-to-leading-log perturbative QCD calculation agrees with the data within the theoretical and experimental uncertainties, with the data/theory ratio of 1.71 +/- 0.02(stat)+/- 0.18(sys) for 0.3 < p(T)< 9 GeV/c. The total charm production cross section at this energy has also been deduced to be sigma(cc)=567 +/- 57(stat)+/- 193(sys) mu b.
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| 6. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 7. |
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| 8. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 9. |
- Wu, X. Y., et al.
(författare)
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1.142 mu m GaAsBi/GaAs Quantum Well Lasers Grown by Molecular Beam Epitaxy
- 2017
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Ingår i: ACS Photonics. - : American Chemical Society (ACS). - 2330-4022. ; 4:6, s. 1322-1326
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Tidskriftsartikel (refereegranskat)abstract
- As a promising new class of near-infrared light emitters, GaAsBi laser diodes (LDs) are considered to have a high energy efficiency and an insensitive temperature dependence of the band gap. In this paper, we realize the longest ever reported lasing wavelength up to 1.142 mu m at room temperature in GaAsBi0.058/GaAs quantum well LDs grown by molecular beam epitaxy. The output power is up to 127 mW at 300 K under pulsed mode. We also demonstrate continuous wave mode operation up to 273 K for the first time. The temperature coefficient of the GaAsBi/GaAs LD is 0.26 nm/K in the temperature range of 77-350 K, lower than that of both InGaAsP/InP and InGaAs/GaAs LDs. The characteristic temperature is extracted to be 139 K in the temperature range of 77-225 K and decreases to 79 K at 225-350 K.
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| 10. |
- Chen, DS, et al.
(författare)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Tidskriftsartikel (refereegranskat)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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| 11. |
- Huang, R., et al.
(författare)
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Prediction and Optimization of WAG Flooding by Using LSTM Neural Network Model in Middle East Carbonate Reservoir
- 2021
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Ingår i: Society of Petroleum Engineers - Abu Dhabi International Petroleum Exhibition and Conference, ADIP 2021. - : Society of Petroleum Engineers.
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Konferensbidrag (refereegranskat)abstract
- Production prediction continues to play an increasingly significant role in reservoir development adjustment and optimization, especially in water-alternating-gas (WAG) flooding. As artificial intelligence continues to develop, data-driven machine learning method can establish a robust model based on massive data to clarify development risks and challenges, predict development dynamic characteristics in advance. This study gathers over 15 years actual data from targeted carbonate reservoir and establishes a robust Long Short-Term Memory (LSTM) neural network prediction model based on correlation analysis, data cleaning, feature variables selection, hyper-parameters optimization and model evaluation to forecast oil production, gas-oil ratio (GOR), and water cut (WC) of WAG flooding. In comparison to traditional reservoir numerical simulation (RNS), LSTM neural networks have a huge advantage in terms of computational efficiency and prediction accuracy. The calculation time of LSTM method is 864% less than reservoir numerical simulation method, while prediction error of LSTM method is 261% less than RNS method. We classify producers into three types based on the prediction results and propose optimization measures aimed at the risks and challenges they faced. Field implementation indicates promising outcome with better reservoir support, lower GOR, lower WC, and stabler oil production. This study provides a novel direction for application of artificial intelligence in WAG flooding development and optimization.
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| 12. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)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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| 13. |
- Ou, H. Y., et al.
(författare)
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Tunable and reconfigurable multi-tap microwave photonic filter with negative coefficients based on a single laser diode
- 2009
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Ingår i: Journal of Optics. A, Pure and applied optics. - : IOP Publishing. - 1464-4258 .- 1741-3567. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- A tunable and reconfigurable multi-tap microwave photonic filter with negative coefficients is proposed and demonstrated. The baseband resonance is eliminated by an electro-optic phase modulator combined with a dispersive medium. A Mach-Zehnder modulator (MZM) is used to get a multi-wavelength source out of a single laser diode. The free spectral range and spectral response of the microwave photonic filter is tuned and reconfigured by controlling the microwave signal and the bias voltage applied on the MZM. Experimental results show the enhanced flexibility of the present microwave photonic filter.
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| 14. |
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| 15. |
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| 16. |
- De Rosa, G., et al.
(författare)
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Velocity-resolved Reverberation Mapping of Five Bright Seyfert 1 Galaxies
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 866:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results from a reverberation-mapping campaign undertaken during the first half of 2012, with additional data on one active galactic nucleus (AGN) (NGC 3227) from a 2014 campaign. Our main goals are (1) to determine the black hole masses from continuum-H beta reverberation signatures, and (2) to look for velocity-dependent time delays that might be indicators of the gross kinematics of the broad-line region. We successfully measure H beta time delays and black hole masses for five AGNs, four of which have previous reverberation mass measurements. The values measured here are in agreement with earlier estimates, though there is some intrinsic scatter beyond the formal measurement errors. We observe velocity-dependent H beta lags in each case, and find that the patterns have changed in the intervening five years for three AGNs that were also observed in 2007.
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| 17. |
- Fu, H. Y., et al.
(författare)
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A tunable and reconfigurable microwave photonic filter based on two cascaded modulators and a dispersive medium
- 2008
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Ingår i: Optics Communications. - : Elsevier BV. - 0030-4018 .- 1873-0310. ; 281:22, s. 5550-5554
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Tidskriftsartikel (refereegranskat)abstract
- A novel tunable and reconfigurable microwave photonic filter based on two cascaded modulators and a dispersive medium is proposed, theoretically discussed and experimentally demonstrated. A single-wavelength LD and a modulator (either a Mach-Zehnder modulator or a phase modulator which can avoid the do bias drift problem) are used to obtain a multi-wavelength optical source. By adjusting the modulation frequency and the bias voltage on the modulators, the wavelength spacing and the relative amplitude of the optical tones change, thus making the filter tunable and reconfigurable. The experimental results show that the proposed filters have good tunability and reconfigurability and the mainlobe-to-sidelobe ratio of around 25 dB is achieved.
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| 18. |
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| 19. |
- He, J., et al.
(författare)
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Development and Evaluation of an Ensemble-Based Data Assimilation System for Regional Reanalysis Over the Tibetan Plateau and Surrounding Regions
- 2019
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Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:8, s. 2503-2522
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Tidskriftsartikel (refereegranskat)abstract
- The Tibetan Plateau is regarded as the Earth's Third Pole, which is the source region of several major rivers that impact more 20% the world population. This high‐altitude region is reported to have been undergoing much greater rate of weather changes under global warming, but the existing reanalysis products are inadequate for depicting the state of the atmosphere, particularly with regard to the amount of precipitation and its diurnal cycle. An ensemble Kalman filter (EnKF) data assimilation system based on the limited‐area Weather Research and Forecasting (WRF) model was evaluated for use in developing a regional reanalysis over the Tibetan Plateau and the surrounding regions. A 3‐month prototype reanalysis over the summer months (June−August) of 2015 using WRF‐EnKF at a 30‐km grid spacing to assimilate nonradiance observations from the Global Telecommunications System was developed and evaluated against independent sounding and satellite observations in comparison to the ERA‐Interim and fifth European Centre for Medium‐Range Weather Forecasts Reanalysis (ERA5) global reanalysis. Results showed that both the posterior analysis and the subsequent 6‐ to 12‐hr WRF forecasts of the prototype regional reanalysis compared favorably with independent sounding observations, satellite‐based precipitation versus those from ERA‐Interim and ERA5 during the same period. In particular, the prototype regional reanalysis had clear advantages over the global reanalyses of ERA‐Interim and ERA5 in the analysis accuracy of atmospheric humidity, as well as in the subsequent downscale‐simulated precipitation intensity, spatial distribution, diurnal evolution, and extreme occurrence.
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| 20. |
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| 21. |
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| 22. |
- Kaiser, M., et al.
(författare)
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Polycrystalline SiC as source material for the growth of fluorescent SiC layers
- 2013
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Ingår i: Silicon Carbide And Related Materials 2012. - : Trans Tech Publications Inc.. - 9783037856246 ; , s. 39-42
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Konferensbidrag (refereegranskat)abstract
- Polycrystalline doped SiC act as source for fluorescent SiC. We have studied the growth of individual grains with different polytypes in the source material. We show an evolution and orientation of grains of different polytypes in polycrystalline SiC ingots grown by the Physical Vapor Transport method. The grain influence on the growth rate of fluorescent SiC layers grown by a sublimation epitaxial process is discussed in respect of surface kinetics.
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| 23. |
- Linnarsson, Margareta K., et al.
(författare)
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Lateral boron distribution in polycrystalline sic source materials
- 2013
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Ingår i: Silicon Carbide And Related Materials 2012. - : Trans Tech Publications Inc.. - 9783037856246 ; , s. 397-400
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Konferensbidrag (refereegranskat)abstract
- Polycrystalline SiC containing boron and nitrogen are used in growth of fluorescent SiC for white LEDs. Two types of doped polycrystalline SiC have been studied in detail with secondary ion mass spectrometry: sintered SiC and poly-SiC prepared by sublimation in a physical vapor transport setup. The materials are co-doped materials with nitrogen and boron to a concentration of 1x1018 cm-3 and 1x1019 cm-3, respectively. Depth profiles as well as ion images have been recorded. According to ocular inspection, the analyzed poly-SiC consists mainly of 4H-SiC and 6H-SiC grains. In these grains, the boron concentration is higher and the nitrogen concentration is lower in the 6H-SiC compared to the 4H-SiC polytype. No inter-diffusion between grains is observed.
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| 24. |
- Ou, H., et al.
(författare)
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Fluorescent SiC for white light-emitting diodes
- 2012
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Ingår i: Asia Commun. Photonics Conf.. - Washington, D.C. : OSA.
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Konferensbidrag (refereegranskat)abstract
- The strong photoluminescence from f-SiC was achieved after the optimization of the B and N concentrations. Surface nanostructures were successfully applied to enhance the extraction efficiency. f-SiC is a promising wavelength convertor for white LEDs.
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| 25. |
- Ou, Y., et al.
(författare)
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Fabrication of broadband antireflective sub-wavelength structures on fluorescent SiC
- 2013
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Ingår i: Materials Science Forum. - 9783037856246 ; , s. 1024-1027
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Konferensbidrag (refereegranskat)abstract
- Surface nanocones on 6H-SiC have been developed and demonstrated as an effective method of enhancing the light extraction efficiency from fluorescent SiC layers. The surface reflectance, measured from the opposite direction of light emission, over a broad bandwidth range is significantly suppressed from 20.5% to 1.0% after introducing the sub-wavelength structures. An omnidirectional light harvesting enhancement (>91%), is also achieved which promotes fluorescent SiC as a good candidate of wavelength converter for white light-emitting diodes
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| 26. |
- Ou, Y., et al.
(författare)
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Photoluminescence and Raman spectroscopy characterization of boron-and nitrogen-doped 6H silicon carbide
- 2012
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Ingår i: Silicon Carbide and Related Materials 2011. - : Trans Tech Publications Inc.. - 9783037854198 ; , s. 233-236
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Konferensbidrag (refereegranskat)abstract
- Nitrogen-boron doped 6H-SiC epilayers grown on low off-axis 6H-SiC substrates have been characterized by photoluminescence and Raman spectroscopy. The photoluminescence results show that a doping larger than 10 18 cm -3 is favorable to observe the luminescence and addition of nitrogen leads to an increased luminescence. A dopant concentration difference larger than 4×10 18 cm -3 is proposed to achieve intense photoluminescence. Raman spectroscopy further confirmed the doping type and concentrations for the samples. The results indicate that N-B doped SiC can serve as a good wavelength converter in white LEDs applications.
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| 27. |
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| 28. |
- Schimmel, S., et al.
(författare)
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Step-flow growth of fluorescent 4H-SiC layers on 4 degree off-axis substrates
- 2013
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Ingår i: Silicon Carbide and Related Materials 2012. - : Trans Tech Publications Inc.. - 9783037856246 ; , s. 185-188
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Konferensbidrag (refereegranskat)abstract
- Homoepitaxial layers of fluorescent 4H-SiC were grown on 4 degree off-axis substrates by sublimation epitaxy. Luminescence in the green spectral range was obtained by co-doping with nitrogen and boron utilizing donor-acceptor pair luminescence. This concept opens possibilities to explore green light emitting diodes using a new materials platform.
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| 29. |
- Schimmel, S., et al.
(författare)
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The role of defects in fluorescent silicon carbide layers grown by sublimation epitaxy
- 2014
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Ingår i: IOP Conference Series. - : Institute of Physics Publishing (IOPP). ; 56:1, s. 012002-
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Konferensbidrag (refereegranskat)abstract
- Donor-acceptor co-doped SiC is a promising light converter for novel monolithic all-semiconductor white LEDs due to its broad-band donor-acceptor pair luminescence and potentially high internal quantum efficiency. Besides sufficiently high doping concentrations in an appropriate ratio yielding short radiative lifetimes, long nonradiative lifetimes are crucial for efficient light conversion. The impact of different types of defects is studied by characterizing fluorescent silicon carbide layers with regard to photoluminescence intensity, homogeneity and efficiency taking into account dislocation density and distribution. Different doping concentrations and variations in gas phase composition and pressure are investigated.
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| 30. |
- Wilhelm, Martin, et al.
(författare)
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Photoluminescence topography of fluorescent SiC and its corresponding source crystals
- 2013
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Ingår i: Silicon Carbide and Related Materials 2012. - : Trans Tech Publications Inc.. ; , s. 421-424
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Konferensbidrag (refereegranskat)abstract
- The preparation and application of co-doped polycrystalline SiC as source in sublimation growth of fluorescent layers is a complex topic. Photoluminescence topographies of luminescent 6H-SiC layers and their corresponding source crystals have been studied in order to investigate the dependence of the epitaxial growth on the source material. It is shown that the homogeneity concerning the dopant incorporation and the layer luminescence intensity does not depend on the characteristics of the PVT grown source material. Therefore co-doped polycrystalline SiC is a promising source material in fast sublimation growth of luminescent 6H-SiC.
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| 31. |
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| 32. |
- Xiong, M., et al.
(författare)
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41.6 Gb/s RZ-DPSK to NRZ-DPSK format conversion in a microring resonator
- 2012
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Ingår i: 2012 17th Opto-Electronics and Communications Conference. ; , s. 891-892
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Konferensbidrag (refereegranskat)abstract
- RZ-DPSK to NRZ-DPSK format conversion in a silicon microring resonator is demonstrated experimentally for the first time at 41.6 Gb/s. The converted signal eye diagrams and bit-error-rate measurements show the good performance of the scheme.
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| 33. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 34. |
- Chen, Deliang, 1961, et al.
(författare)
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Satellite measurements reveal strong anisotropy in spatial coherence of climate variations over the Tibet Plateau
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- This study uses high-resolution, long-term satellite observations to evaluate the spatial scales of the climate variations across the Tibet Plateau (TP). Both land surface temperature and precipitation observations of more than 10 years were analysed with a special attention to eight existing ice-core sites in the TP. The temporal correlation for the monthly or annual anomalies between any two points decreases exponentially with their spatial distance, and we used the e-folding decay constant to quantify the spatial scales. We found that the spatial scales are strongly direction-dependent, with distinctive patterns in the west-east and south-north orientations, for example. Meanwhile, in the same directions the scales are largely symmetric backward and forward. Focusing on the west-east and south-north directions, we found the spatial coherence in the first is generally stronger than in the second. The annual surface temperature had typical spatial scales of 302-480 km, while the annual precipitation showed smaller scales of 111-182 km. The majority of the eight ice-core sites exhibit scales much smaller than the typical scales over the TP as a whole. These results provide important observational basis for the selection of appropriate downscaling strategies, deployment of climate-data collection networks, and interpreting paleoclimate reconstructions.
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| 35. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 36. |
- Fischer, Alexander W., et al.
(författare)
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Lysosomal lipoprotein processing in endothelial cells stimulates adipose tissue thermogenic adaptation
- 2021
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Ingår i: Cell Metabolism. - : Elsevier. - 1550-4131 .- 1932-7420. ; 33:3, s. 547-564.e7
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Tidskriftsartikel (refereegranskat)abstract
- In response to cold exposure, thermogenic adipocytes internalize large amounts of fatty acids after lipoprotein lipase-mediated hydrolysis of triglyceride-rich lipoproteins (TRL) in the capillary lumen of brown adipose tissue (BAT) and white adipose tissue (WAT). Here, we show that in cold-exposed mice, vascular endothelial cells in adipose tissues endocytose substantial amounts of entire TRL particles. These lipoproteins subsequently follow the endosomal-lysosomal pathway, where they undergo lysosomal acid lipase (LAL)-mediated processing. Endothelial cell-specific LAL deficiency results in impaired thermogenic capacity as a consequence of reduced recruitment of brown and brite/beige adipocytes. Mechanistically, TRL processing by LAL induces proliferation of endothelial cells and adipocyte precursors via beta-oxidation-dependent production of reactive oxygen species, which in turn stimulates hypoxia-inducible factor-1α-dependent proliferative responses. In conclusion, this study demonstrates a physiological role for TRL particle uptake into BAT and WAT and establishes endothelial lipoprotein processing as an important determinant of adipose tissue remodeling during thermogenic adaptation.
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| 37. |
- Fu, Hongyan, et al.
(författare)
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A tunable single-passband microwave photonic filter with positive and negative taps using a fiber Mach-Zehnder interferometer and phase modulation
- 2010
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Ingår i: Optics and Laser Technology. - : Elsevier BV. - 0030-3992 .- 1879-2545. ; 42:1, s. 81-84
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a tunable single-passband microwave photonic filter with positive and negative taps based on phase modulation and a fiber Mach-Zehnder interferometer (FMZI)) is presented, theoretically analyzed and experimentally demonstrated. The FMZI as the slicing filter results in a single-bandpass characteristic for the presented filter, and by using phase modulation, a number of negative taps are generated, thus making the baseband resonance suppressed, which is desirable for microwave photonic filter's application. The wavelength spacing of the FMZI can be tuned by employing an optical variable delay line, making the present filter continuously tunable. A tunable single-passband microwave photonic filter without baseband resonance is achieved in the experiment. The present filter shows an extinction ratio of up to similar to 20dB and good tuning linearity.
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| 38. |
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| 39. |
- Huang, Joyce Y., et al.
(författare)
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Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2394-2405
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Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
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- Jung, Audrey Y, et al.
(författare)
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Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes : pooled analysis of population-based studies
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:12, s. 1706-1719
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided.RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
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| 43. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 44. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 48. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 50. |
- Linderholm, Hans W., 1968, et al.
(författare)
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Interannual teleconnections between the summer North Atlantic Oscillation and the East Asian summer monsoon
- 2011
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 116:D13
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a study of the relationship between July–August (JA) mean climate over China, which is strongly linked to the East Asian summer monsoon (EASM), and the summer (JA) North Atlantic Oscillation (SNAO). The variations of temperature, precipitation, and cloud cover related to the SNAO were analyzed for the period 1951–2002 using gridded data sets as well as instrumental data from 160 stations in China. It was shown that the major patterns of summer climate over China are highly connected with the interannual variation of the SNAO, supporting a teleconnection between the North Atlantic region and East Asia. Based on the analyses of the daily and monthly reanalysis data sets, we propose possible mechanisms of this teleconnection. Changes in the position of the North Atlantic storm tracks and transient eddy activity associated with the positive (negative) SNAO phase contribute downstream to negative (positive) sea level pressure anomalies in northeastern East Asia. In negative SNAO years, a stationary wave pattern is excited from the southern SNAO center over northwestern Europe to northeastern East Asia. However, during positive SNAO years, a stationary wave pattern is excited extending from the SNAO center across the central Eurasian continent at around 40°N and downstream to the southeast. This may explain a connection between the positive SNAO and atmospheric circulation in middle and southeastern China.
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