| 1. |
- Chen, Zhi-Qiang, et al.
(författare)
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Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis
- 2021
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genome-wide association studies (GWAS) identify loci underlying the variation of complex traits. One of the main limitations of GWAS is the availability of reliable phenotypic data, particularly for long-lived tree species. Although an extensive amount of phenotypic data already exists in breeding programs, accounting for its high heterogeneity is a great challenge. We combine spatial and factor-analytics analyses to standardize the heterogeneous data from 120 field experiments of 483,424 progenies of Norway spruce to implement the largest reported GWAS for trees using 134 605 SNPs from exome sequencing of 5056 parental trees.Results: We identify 55 novel quantitative trait loci (QTLs) that are associated with phenotypic variation. The largest number of QTLs is associated with the budburst stage, followed by diameter at breast height, wood quality, and frost damage. Two QTLs with the largest effect have a pleiotropic effect for budburst stage, frost damage, and diameter and are associated with MAP3K genes. Genotype data called from exome capture, recently developed SNP array and gene expression data indirectly support this discovery.Conclusion: Several important QTLs associated with growth and frost damage have been verified in several southern and northern progeny plantations, indicating that these loci can be used in QTL-assisted genomic selection. Our study also demonstrates that existing heterogeneous phenotypic data from breeding programs, collected over several decades, is an important source for GWAS and that such integration into GWAS should be a major area of inquiry in the future.
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| 2. |
- Dong, Chuanjiang, et al.
(författare)
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The Assessment on Synergistic Activity of Ebselen and Silver Ion Against Yersinia pseudotuberculosis
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Yersinia pseudotuberculosis is a foodborne zoonotic bacterium that is pathogenic to guinea pigs, rabbits, and mice. It also causes pseudotuberculosis in humans. However, it still lacked the scientific basis for control. Here, we found out that Ebselen (EbSe) exhibited synergistic antibacterial activity with silver nitrate (Ag+) against Y. pseudotuberculosis YpIII strain with high efficacy in vitro using UV-visible light absorption spectrum, 5,5’-dithiobis-(2-nitrobenzoic acid), laser scanning confocal microscope, flow cytometry, transmission electron microscopy and Western blotting assays. The depletion of total glutathione (GSH) amount and inhibition of thioredoxin reductase (TrxR) activity in thiol-dependent redox system revealed the destructiveness of EbSe-Ag+-caused intracellular oxidative stress. Furthermore, a YpIII-caused mice gastroenteritis model was constructed. EbSe-Ag+ significantly reduced bacterial loads with low toxicity. It also down-regulated the expression levels of interferon (IL)-1β and tumor necrosis factor-α, up-regulated the expression level of IL-10 on-site. All the in vivo results demonstrated the antibacterial activity and immune-modulatory property of EbSe-Ag+. Collectively, these results provided academic fundament for further analysis and development of EbSe-Ag+ as the antibacterial agents for pseudotuberculosis control.
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| 3. |
- Wang, Yan, et al.
(författare)
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Synergy of orographic drag parameterization and high resolution greatly reduces biases of WRF-simulated precipitation in central Himalaya
- 2020
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 54:3-4, s. 1729-40
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Tidskriftsartikel (refereegranskat)abstract
- Current climate models often have significant wet biases in the Tibetan Plateau and encounter particular difficulties in representing the climatic effect of the Central Himalaya Mountain (CHM), where the gradient of elevation is extremely steep and the terrain is complex. Yet, there were few studies dealing with the issue in the high altitudes of this region. In order to improve climate modeling in this region, a network consisting of 14 rain gauges was set up at elevations >2800 m above sea level along a CHM valley. Numerical experiments with Weather Research and Forecasting model were conducted to investigate the effects of meso- and micro-scale terrain on water vapor transport and precipitation. The control case uses a high horizontal resolution (0.03°) and a Turbulent Orographic Form Drag (TOFD) scheme to resolve the mesoscale terrain and to represent sub-grid microscale terrain effect. The effects of the horizontal resolution and the TOFD scheme were then analyzed through comparisons with sensitivity cases that either use a low horizontal resolution (0.09°) or switch off the TOFD scheme. The results show that the simulations with high horizontal resolution, even without the TOFD scheme, can not only increase the spatial consistency (correlation coefficient 0.84–0.92) between the observed and simulated precipitation, but also considerably reduce the wet bias by more than 250%. Adding the TOFD scheme further reduces the precipitation bias by 50% or so at almost all stations in the CHM. The TOFD scheme reduces precipitation intensity, especially heavy precipitation (>10 mm h−1) over high altitudes of the CHM. Both high horizontal resolution and TOFD enhance the orographic drag to slow down wind; as a result, less water vapor is transported from lowland to the high altitudes of CHM, causing more precipitation at lowland area of the CHM and less at high altitudes of CHM. Therefore, in this highly terrain-complex region, it is crucial to use a high horizontal resolution to depict mesoscale complex terrain and a TOFD scheme to parameterize the drag caused by microscale complex terrain.
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| 4. |
- Feng, Hongliang, et al.
(författare)
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Association between accelerometer-measured amplitude of rest-activity rhythm and future health risk : a prospective cohort study of the UK Biobank
- 2023
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Ingår i: The Lancet Healthy Longevity. - 2666-7568. ; 4:5, s. e200-e210
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The health effects of rest-activity rhythm are of major interest to public health, but its associations with health outcomes remain elusive. We aimed to examine the associations between accelerometer-measured rest-activity rhythm amplitude and health risks among the general UK population.METHODS: We did a prospective cohort analysis of UK Biobank participants aged 43-79 years with valid wrist-worn accelerometer data. Low rest-activity rhythm amplitude was defined as the first quintile of relative amplitude; all other quintiles were classified as high rest-activity rhythm amplitude. Outcomes of interest were defined using International Classification of Diseases 10th Revision codes and consisted of incident cancer and cardiovascular, infectious, respiratory, and digestive diseases, and all-cause and disease-specific (cardiovascular, cancer, and respiratory) mortality. Participants with a current diagnosis of any outcome of interest were excluded. We assessed the associations between decreased rest-activity rhythm amplitude and outcomes using Cox proportional hazards models.FINDINGS: Between June 1, 2013, and Dec 23, 2015, 103 682 participants with available raw accelerometer data were enrolled. 92 614 participants (52 219 [56·4%] women and 40 395 [42·6%] men) with a median age of 64 years (IQR 56-69) were recruited. Median follow-up was 6·4 years (IQR 5·8-6·9). Decreased rest-activity rhythm amplitude was significantly associated with increased incidence of cardiovascular diseases (adjusted hazard ratio 1·11 [95% CI 1·05-1·16]), cancer (1·08 [1·01-1·16]), infectious diseases (1·31 [1·22-1·41]), respiratory diseases (1·26 [1·19-1·34]), and digestive diseases (1·08 [1·03-1·14]), as well as all-cause mortality (1·54 [1·40-1·70]) and disease-specific mortality (1·73 [1·34-2·22] for cardiovascular diseases, 1·32 [1·13-1·55] for cancer, and 1·62 [1·25-2·09] for respiratory diseases). Most of these associations were not modified by age older than 65 years or sex. Among 16 accelerometer-measured rest-activity parameters, low rest-activity rhythm amplitude had the strongest or second- strongest associations with nine health outcomes.INTERPRETATION: Our results suggest that low rest-activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest-activity rhythm to improve health and longevity.
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| 5. |
- Feng, Hongliang, et al.
(författare)
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Associations of timing of physical activity with all-cause and cause-specific mortality in a prospective cohort study
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.
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| 6. |
- Hou, Juan, et al.
(författare)
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Helium bubble nucleation in Laser Powder Bed Fusion processed 304L stainless steel
- 2020
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115. ; 542
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Tidskriftsartikel (refereegranskat)abstract
- The interest in application of Additive Manufacturing (AM) to nuclear industry stems not only from the benefits of design freedom and shortened lead time, but also from the possibility of enhancing the performance through microstructure control. One of the most important requirements for in-core structural material in nuclear power plants is helium resistance. The Laser Powder Bed Fusion (LPBF) processed 304L stainless steel possesses strong defect sinks such as high densities of dislocation-surrounded sub-grains and dispersed nano-inclusions. In this work the LPBF processed 304L in as-built and solution-annealed conditions along with a conventionally rolled counterpart were implanted with 350 keV He+ ion at 300 °C to 0.24 dpa (displacement per atom). Transmission Electron Microscopy (TEM) observations indicate significantly higher helium resistance of the as-built LPBF 304L compared to the other two samples. The sink strengths in the three samples are calculated based on the measurements of the microstructural features using simplified equations for the correlation between microstructural characteristics and helium tolerance. Based on the calculation, the cellular sub-grains and the dispersed nano-inclusions are the primary and secondary contributors to the helium resistance of LPBF 304L steel.
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| 7. |
- Lin, Zhipeng, et al.
(författare)
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Electrocatalyzed direct arene alkenylations without directing groups for selective late-stage drug diversification
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemistry has emerged as an increasingly viable tool in molecular synthesis. Here the authors realize electrocatalyzed C-H activations, with the aid of data science and artificial intelligence, towards selective alkenylations for late-stage drug diversifications. Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrochemical C-H activations, these arene functionalizations generally require directing groups to enable the C-H activation. The installation and removal of these directing groups call for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C-H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrochemical C-H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. A physical organic parameter-based machine learning model was developed to predict position-selectivity in electrochemical C-H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C-H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations.
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| 8. |
- Ling, Yiming, et al.
(författare)
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Observations of Kelvin-Helmholtz Waves in the Earth's Magnetotail Near the Lunar Orbit
- 2018
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 123:5, s. 3836-3847
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Tidskriftsartikel (refereegranskat)abstract
- Kelvin‐Helmholtz waves (KHWs), which have been widely observed at the magnetopause in the region near the Earth, play an essential role in the transport of solar wind plasma and energy into the magnetosphere under dominantly northward interplanetary magnetic field (IMF) conditions. In this study, we present simultaneous observations of KHWs under the northward IMF observed by both the Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) spacecraft in the Earth's magnetotail around the lunar orbit (at X ~ −50RE, Y ~ 30RE, dusk side) and the Geotail in the near‐Earth space (at X ~ −5RE, Y ~ −10RE, dawn side). The KHWs are quantitatively characterized by their dominant period, phase velocity, and wavelength, utilizing wavelet analysis and an approximation of their center‐of‐mass velocity. Our results suggest that the phase velocity and spatial scale of KHWs may increase as they propagate along the boundary layer toward the tail. Alternatively, the differences between the ARTEMIS and Geotail observations may indicate the possibility of dawn‐dusk asymmetry in the excited KHWs in this study. Our results strongly evidence the existence of the development of KHWs in terms of their wave frequency and scale size in the magnetotail and provide insight to the time evolution of KHWs along the magnetopause.
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| 9. |
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| 10. |
- Perspicace, Enrico, et al.
(författare)
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Design, synthesis and biological evaluation of new classes of thieno[3,2-d]pyrimidinone and thieno[1,2,3]triazine as inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2).
- 2013
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 63, s. 765-81
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Tidskriftsartikel (refereegranskat)abstract
- Driven by a multidisciplinary approach combination (Structure-Based (SB) Three-Dimensional Quantitative Structure-Activity Relationships (3-D QSAR), molecular modeling, organic chemistry and various biological evaluations) here is reported the disclosure of new thienopyrimidines 1-3 as inhibitors of KDR activity and human umbilical vein endothelial cell (HUVEC) proliferation. More specifically, compound 2f represents a new lead compound that inhibits VEGFR-2 and HUVEC at μM concentration. Moreover by the mean of an endothelial cell tube formation in vitro model 2f tartaric acid salt proved to block angiogenesis of HUVEC at μM level.
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| 11. |
- Wang, Yan, et al.
(författare)
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The Formation of a Dry-Belt in the North Side of Central Himalaya Mountains
- 2019
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 46, s. 2993-3000
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Tidskriftsartikel (refereegranskat)abstract
- ©2019. American Geophysical Union. All Rights Reserved. South Asian monsoon crosses the Himalayan Mountains (HMs) and brings moisture for precipitations in the South Tibetan Plateau. A distinct dry-belt was found in the north of the central HM region, where there are the highest and steepest mountains in the world. Through in situ and remote-sensing observations and convection-permitting numerical experiments, the current study demonstrates that the formation of the dry-belt is mainly due to the depletion of water vapor when the monsoonal flow climbs the steep south slope of the HMs. The foehn phenomenon is notable over the north slope of the HMs, but the hot and dry downslope flow does not significantly reduce the amount of the precipitation; instead, it can delay the peak of the diurnal precipitation in the north side of the HMs.
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| 12. |
- Yang, Lulu, et al.
(författare)
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Association of accelerometer-derived circadian abnormalities and genetic risk with incidence of atrial fibrillation
- 2023
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Ingår i: npj Digital Medicine. - : Springer Nature. - 2398-6352. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests potential links between circadian rhythm and atrial fibrillation (AF). However, whether circadian disruption can predict the onset of AF in the general population remains largely unknown. We aim to investigate the association of accelerometer-measured circadian rest-activity rhythm (CRAR, the most prominent circadian rhythm in humans) with the risk of AF, and examine joint associations and potential interactions of CRAR and genetic susceptibility with AF incidence. We include 62,927 white British participants of UK Biobank without AF at baseline. CRAR characteristics, including amplitude (strength), acrophase (timing of peak activity), pseudo-F (robustness), and mesor (height), are derived by applying an extended cosine model. Genetic risk is assessed with polygenic risk scores. The outcome is the incidence of AF. During a median follow-up of 6.16 years, 1920 participants developed AF. Low amplitude [hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.25-1.58], delayed acrophase (HR: 1.24, 95% CI: 1.10-1.39), and low mesor (HR: 1.36, 95% CI: 1.21-1.52), but not low pseudo-F, are significantly associated with a higher risk of AF. No significant interactions between CRAR characteristics and genetic risk are observed. Joint association analyses reveal that participants with unfavourable CRAR characteristics and high genetic risk yield the highest risk of incident AF. These associations are robust after controlling for multiple testing and in a series of sensitivity analyses. Accelerometer-measured CRAR abnormalities, characterized by decreased strength and height, and later timing of peak activity of circadian rhythm, are associated with a higher risk of AF in the general population.
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