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- 2019
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 7. |
- 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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| 8. |
- Li, Jing, et al.
(författare)
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An obligatory role for neurotensin in high-fat-diet-induced obesity
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533, s. 411-415
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually and are among the most prevalent and challenging conditions confronting the medical profession. Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine and released by fat ingestion, facilitates fatty acid translocation in rat intestine, and stimulates the growth of various cancers. The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively). Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality; however, a role for NT as a causative factor in these diseases is unknown. Here we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin). Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and suggest that NT may provide a prognostic marker of future obesity and a potential target for prevention and treatment.
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| 9. |
- Qian, Deping, et al.
(författare)
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Design rules for minimizing voltage losses in high-efficiency organic solar cells
- 2018
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Ingår i: Nature Materials. - : NATURE PUBLISHING GROUP. - 1476-1122 .- 1476-4660. ; 17:8, s. 703-
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Tidskriftsartikel (refereegranskat)abstract
- The open-circuit voltage of organic solar cells is usually lower than the values achieved in inorganic or perovskite photovoltaic devices with comparable bandgaps. Energy losses during charge separation at the donor-acceptor interface and non-radiative recombination are among the main causes of such voltage losses. Here we combine spectroscopic and quantum-chemistry approaches to identify key rules for minimizing voltage losses: (1) a low energy offset between donor and acceptor molecular states and (2) high photoluminescence yield of the low-gap material in the blend. Following these rules, we present a range of existing and new donor-acceptor systems that combine efficient photocurrent generation with electroluminescence yield up to 0.03%, leading to non-radiative voltage losses as small as 0.21 V. This study provides a rationale to explain and further improve the performance of recently demonstrated high-open-circuit-voltage organic solar cells.
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| 10. |
- 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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| 11. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 12. |
- Zhang, Shuangsheng, et al.
(författare)
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Optimization of Well Position and Sampling Frequency for Groundwater Monitoring and Inverse Identification of Contamination Source Conditions Using Bayes’ Theorem
- 2019
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Ingår i: CMES - Computer Modeling in Engineering & Sciences. - : Tech Science Press. - 1526-1492 .- 1526-1506. ; 119:2, s. 373-394
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Tidskriftsartikel (refereegranskat)abstract
- Coupling Bayes’ Theorem with a two-dimensional (2D) groundwater solute advection-diffusion transport equation allows an inverse model to be established to identify a set of contamination source parameters including source intensity (M ), release location ( X0 , Y0) and release time (T0), based on monitoring well data. To address the issues of insufficient monitoring wells or weak correlation between monitoring data and model parameters, a monitoring well design optimization approach was developed based on the Bayesian formula and information entropy. To demonstrate how the model works, an exemplar problem with an instantaneous release of a contaminant in a confined groundwater aquifer was employed. The information entropy of the model parameters posterior distribution was used as a criterion to evaluate the monitoring data quantity index. The optimal monitoring well position and monitoring frequency were solved by the two-step Monte Carlo method and differential evolution algorithm given a known well monitoring locations and monitoring events. Based on the optimized monitoring well position and sampling frequency, the contamination source was identified by an improved Metropolis algorithm using the Latin hypercube sampling approach. The case study results show that the following parameters were obtained: 1) the optimal monitoring well position (D) is at (445, 200); and 2) the optimal monitoring frequency (Δt) is 7, providing that the monitoring events is set as 5 times. Employing the optimized monitoring well position and frequency, the mean errors of inverse modeling results in source parameters (M, X0 ,Y0 ,T0 ) were 9.20%, 0.25%, 0.0061%, and 0.33%, respectively. The optimized monitoring well position and sampling frequency can effectively safeguard the inverse modeling results in identifying the contamination source parameters. It was also learnt that the improved Metropolis-Hastings algorithm (a Markov chain Monte Carlo method) can make the inverse modeling result independent of the initial sampling points and achieves an overall optimization, which significantly improved the accuracy and numerical stability of the inverse modeling results.
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| 13. |
- An, Bolun, et al.
(författare)
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An approach to evaluate wheel-rail match properties considering the flexibility of ballastless track : Comparison of rigid and flexible track models in wheel-rail profile matching
- 2019
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Ingår i: International Journal of COMADEM. - : COMADEM International. - 1363-7681. ; 22:3, s. 5-13
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Tidskriftsartikel (refereegranskat)abstract
- Many different wheel/rail profiles are used in the China high-speed railway, and vehicle operation safety and comfort will decrease if the inappropriate wheel-rail profile pair is used. To solve the problem of estimating the wheel-rail match, many numerical models, including vehicle system dynamic models and wheel-rail rolling contact models, have been established to analyse the wheel-rail dynamic responses. Both methods have less consideration of the flexibility and vibration characteristics of ballastless track, leading to deviations in the calculation of middle and high frequency vibration. This paper proposes a vehicle-flexible track coupling model and compares it with the vehicle dynamic model (vehicle-rigid track model). In the rigid track model, only the track irregularities are considered in the track module; the vibrations and deformations of rails, track slab and the foundation are considered in the flexible track model. Taking Chinese CRH3 series wheel profile S1002CN and rail profile CHN60 as examples and considering different track excitations, the two models are compared. The wheel-rail interaction forces, wheel-rail wear depths, wear volumes and vehicle accelerations are chosen as analysis indices for the comparative study.The results show that the wheel-rail forces of the flexible track model are larger than the rigid track model in the frequency range from 70 to 120Hz, while they decrease obviously in the frequency range above 150Hz. The differences in wear depths and volumes between the two models exceed 10%. Therefore, the flexible track model should be considered when studying the match properties of different wheel-rail pairs.
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| 14. |
- Chen, Hong, et al.
(författare)
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PKU-3 : An HCI-Inclusive Aluminoborate for Strecker Reaction Solved by Combining RED and PXRD
- 2015
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 137:22, s. 7047-7050
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Tidskriftsartikel (refereegranskat)abstract
- A novel microporous aluminoborate, denoted as PKU-3, was prepared by the boric acid flux method. The structure of PKU-3 was determined by combining the rotation electron diffraction and synchrotron powder X-ray diffraction data with well resolved ordered Cl- ions in the channel. Composition and crystal structure analysis showed that there are both proton and chlorine ions in the channels. Part of these protons and chlorine ions can be washed away by basic solutions to activate the open pores. The washed PKU-3 can be used as an efficient catalyst in the Strecker reaction with yields higher than 90%.
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| 15. |
- Cheng, Li-Peng, et al.
(författare)
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Efficient CsPbBr3 Perovskite Light-Emitting Diodes Enabled by Synergetic Morphology Control
- 2019
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Ingår i: Advanced Optical Materials. - : WILEY-V C H VERLAG GMBH. - 2162-7568 .- 2195-1071. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- The development of solution-processed inorganic metal halide perovskite light-emitting diodes (PeLEDs) is currently hindered by low emission efficiency due to morphological defects and severe non-radiative recombination in all-inorganic perovskite emitters. Herein, bright PeLEDs are demonstrated by synergetic morphology control over cesium lead bromide (CsPbBr3) perovskite films with the combination of two additives. The phenethylammonium bromide additive enables the formation of mixed-dimensional CsPbBr3 perovskites featuring the reduced grain size (amp;lt;15 nm) and efficient energy funneling, while the dielectric polyethyleneglycol additive promotes the formation of highly compact and pinhole-free perovskite films with defect passivation at grain boundaries. Consequently, green PeLEDs achieve a current efficiency of 37.14 cd A(-1) and an external quantum efficiency of 13.14% with the maximum brightness up to 45 990 cd m(-2) and high color purity. Furthermore, this method can be effectively extended to realize flexible PeLEDs on plastic substrates with a high efficiency of 31.0 cd A(-1).
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| 16. |
- Cui, Yong, et al.
(författare)
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Over 16% efficiency organic photovoltaic cells enabled by a chlorinated acceptor with increased open-circuit voltages
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Broadening the optical absorption of organic photovoltaic (OPV) materials by enhancing the intramolecular push-pull effect is a general and effective method to improve the power conversion efficiencies of OPV cells. However, in terms of the electron acceptors, the most common molecular design strategy of halogenation usually results in down-shifted molecular energy levels, thereby leading to decreased open-circuit voltages in the devices. Herein, we report a chlorinated non-fullerene acceptor, which exhibits an extended optical absorption and meanwhile displays a higher voltage than its fluorinated counterpart in the devices. This unexpected phenomenon can be ascribed to the reduced non-radiative energy loss (0.206 eV). Due to the simultaneously improved short-circuit current density and open-circuit voltage, a high efficiency of 16.5% is achieved. This study demonstrates that finely tuning the OPV materials to reduce the bandgap-voltage offset has great potential for boosting the efficiency.
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| 17. |
- 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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| 18. |
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| 19. |
- Ding-Mastera, Jing, et al.
(författare)
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A latent-class adaptive routing choice model in stochastic time-dependent networks
- 2019
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Ingår i: Transportation Research Part B. - : Elsevier. - 0191-2615 .- 1879-2367. ; 124, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Transportation networks are inherently uncertain due to random disruptions; meanwhile, real-time information potentially helps travelers adapt to realized traffic conditions and make better route choices under such disruptions. Modeling adaptive route choice behavior is essential in evaluating real-time traveler information systems and related policies. This research contributes to the state of the art by developing a latent-class routing policy choice model in a stochastic time-dependent network with revealed preference data. A routing policy is defined as a decision rule applied at each link that maps possible realized traffic conditions to decisions on the link to take next. It represents a traveler's ability to look ahead in order to incorporate real-time information not yet available at the time of decision. A case study is conducted in Stockholm, Sweden and data for the stochastic time-dependent network are generated from hired taxi Global Positioning System (GPS) readings. A latent-class Policy Size Logit model is specified, with routing policy users who follow routing policies and path users who follow fixed paths. Two additional layers of latency in the measurement equation are accounted for: 1) the choice of a routing policy is latent and only its realized path on a given day can be observed; and 2) when GPS readings have relatively long gaps, the realized path cannot be uniquely identified, and the likelihood of observing vehicle traces with non-consecutive links is instead maximized. Routing policy choice set generation is based on the generalization of path choice set generation methods. The generated choice sets achieve 95% coverage for 100% overlap threshold after correcting GPS mistakes and breaking up trips with intermediate stops, and further achieve 100% coverage for 90% overlap threshold. Estimation results show that the routing policy user class probability increases with trip length, and the latent-class routing policy choice model fits the data better than a single-class path choice or routing policy choice model. This suggests that travelers are heterogeneous in terms of their ability and/or willingness to plan ahead and utilize real-time information, and an appropriate route choice model for uncertain networks should take into account the underlying stochastic travel times and structured traveler heterogeneity in terms of real-time information utilization.
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| 20. |
- Gao, Jiajia, et al.
(författare)
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Light-induced electrolyte improvement in cobalt tris(bipyridine)-mediated dye-sensitized solar cells
- 2019
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 7:33, s. 19495-19505
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Tidskriftsartikel (refereegranskat)abstract
- Lithium-ion-free tris(2,2′-bipyridine) Co(ii/iii)-mediated electrolytes have previously been proposed for long-term stable dye-sensitized solar cells (DSSCs). Such redox systems also offer an impressive DSSC performance improvement under light soaking exposure, manifested by an increase in photocurrent and fill factor without the expense of decreasing photovoltage. Kinetic studies show that charge transfer and ion diffusion at the electrode/electrolyte interface are improved due to the light exposure. Control experiments reveal that the light effect is unambiguously associated with electrolyte components, [Co(bpy)3]3+ and the Lewis-base additive tert-butylpyridine (TBP). Electrochemical and spectroscopic investigation of the [Co(bpy)3]3+/TBP mixtures points out that the presence of TBP, which retards the electrolyte diffusion, however causes an irreversible redox reaction of [Co(bpy)3]3+ upon light exposure that improves the overall conductivity. This discovery not only provides a new strategy to mitigate the typical Jsc-Voc trade-off in Co(ii/iii)-mediated DSSCs but also highlights the importance of investigating the photochemistry of a photoelectrochemical system.
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| 21. |
- Gao, Jing, et al.
(författare)
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Solar Water Splitting with Perovskite/Silicon Tandem Cell and TiC-Supported Pt Nanocluster Electrocatalyst
- 2019
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Ingår i: Joule. - : CELL PRESS. - 2542-4351. ; 3:12, s. 2930-2941
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Tidskriftsartikel (refereegranskat)abstract
- Developing efficient, stable, and cost-effective photosystems to split water into hydrogen and oxygen using sunlight is of paramount importance for future production of fuels and chemicals from renewable sources. However, the high cost of current systems limits their widespread application. Here, we developed a highly efficient TiC-supported Pt nanocluster catalyst for hydrogen evolution reaction that rivals the commercial Pt/C catalyst with 5 times less Pt loading. Combining with the NiFe-layered double hydroxide for oxygen evolution reaction and driven for the first time by a monolithic perovskite/silicon tandem solar cell, we achieved a solar water splitting system with 18.7% solar-to-hydrogen conversion efficiency, setting a record for water splitting systems with earth-abundant and inexpensive photo-absorbers.
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| 22. |
- Gao, Kai, et al.
(författare)
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Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring
- 2015
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Ingår i: Huanjing Kexue. - 0250-3301. ; 36:10, s. 3878-3883
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Tidskriftsartikel (refereegranskat)abstract
- CYP1 subfamily genes in gills and liver of rainbow trout as biomarkers were studied to establish methods for quantitative mRNA expression analysis of these genes and to determine their expression pattern. Fish caged in various waters in the Haihe River (Tianjin) were analyzed. The mRNA expression patterns observed in Machangjian River and estuary site of Haihe River were markedly similar but at different levels, reflecting that those sites shared the similar pollution components but with different local pollution load. CYP1C1 and 1C3 were only induced at Gegu site and estuary site of Haihe River, indicating different types of CYP1 agonists in Machangjian River. Response patterns of multiple CYP1 genes in gills and liver could be applied in the monitoring strategy. The response patterns of CYP1 genes could be used for better understanding the relationship between complex mixtures of pollutants and biological response of organisms in aquatic environments.
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| 23. |
- Gao, Shang, 1982-, et al.
(författare)
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An Empirical Study on Users' Continuous Usage Intention of QR Code Mobile Payment Services in China
- 2018
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Ingår i: International Journal of E-Adoption (IJEA). - : IGI Global. - 1937-9633 .- 1937-9641. ; 10:1, s. 18-33
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Tidskriftsartikel (refereegranskat)abstract
- This article aims to investigate users' continuous usage intention of quick response (QR) code mobile payment services in China. Drawing from UTAUT as theory foundation, this study integrates with literature on perceived risk and involvement to propose a research model and seven research hypotheses to examine user's continuous usage of QR code mobile payment services. The research model was empirically tested with a sample of 215 users of QR code mobile payment services in China. The results indicated that five of seven research hypotheses were significantly supported. According to the results, performance expectancy, effort expectancy and social influence had significant positive direct impacts on users' continuous usage intention of QR code mobile payment services. However, perceived risk did not have a negative effect on users' continuous usage intention of QR code mobile payment services. This article contributes to the existing literature on continuous usage of mobile payment services.
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| 24. |
- Gao, Sanshuang, et al.
(författare)
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Selective voltammetric determination of Cd(II) by using N,S-codoped porous carbon nanofibers
- 2018
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Ingår i: Microchimica Acta. - : Springer. - 0026-3672 .- 1436-5073. ; 185
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Tidskriftsartikel (refereegranskat)abstract
- Porous carbon nanofibers codoped with nitrogen and sulfur (NFs) were prepared by pyrolysis of trithiocyanuric acid, silica nanospheres and polyacrylonitrile (PAN) followed by electrospinning. The NFs were used to modify a glassy carbon electrode (GCE) which then displayed highly sensitive response to traces of Cd(II). Compared to a bare GCE and a Nafion modified GCE, the GCE modified with codoped NFs shows improved sensitivity for Cd(II) in differential pulse anodic sweep voltammetry. The stripping peak current (typically measured at 0.81 V vs. Ag/AgCl) increases linearly in the 2.0–500 μg·L−1 Cd(II) concentration range. This is attributed to the large surface area (109 m2·g−1), porous structure, and high fraction of heteroatoms (19 at.% of N and 0.75 at.% of S). The method was applied to the determination of Cd(II) in (spiked) tap water where it gave recoveries that ranged between 96% and 103%.
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| 25. |
- Gao, Sanshuang, et al.
(författare)
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Sensitive and Selective Differential Pulse Voltammetry Detection of Cd(II) and Pb(II) Using Nitrogen-Doped Porous Carbon Nanofiber Film Electrode
- 2017
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Ingår i: Journal of the Electrochemical Society. - : Electrochemical Society. - 0013-4651 .- 1945-7111. ; 164:13, s. H967-H974
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Tidskriftsartikel (refereegranskat)abstract
- Carbon matrix materials are regarded as one of the most important electrode materials for heavy metal detection. But even so, optimization procedures of carbon nanofibers (CNFs) for tracing Cd(II) and Pb(II) remains challenging. Here, zeolitic imidazolate framework (ZIF-8)/polyacrylonitrile (PAN)-derived nitrogen-doped porous carbon nanofibers (N-PCNFs) were investigated as a new electrode material for determining the concentration of Cd(II) and Pb(II). By optimizing electrochemical conditions such as deposition potential, deposition time, pH of buffer solution, and quantity of N-PCNFs loaded on a glassy carbon electrode (GCE), the linear response curves of Cd(II) and Pb(II) could be obtained. Due to the unique structural feature and N content, the N-PCNFs possess excellent detection limits of 0.8 mu g L-1 for Cd(II) and 0.3 mu g L-1 for Pb(II) (S/N = 3). To manifest the practical use of the sensor platform the concentration of Cd(II) and Pb(II) in normal tap and waste water were monitored. According to the ICP-MS results, the calculated recovery (97.0-107%) indicates that N-PCNFs have potential as a candidate material to monitor the concentration of Cd(II) and Pb(II) in practical samples.
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| 26. |
- Gao, Shang, 1982-, et al.
(författare)
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The Role of trust with car-sharing services in the sharing economy in China : From the consumers'€™ perspective
- 2017
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Ingår i: Cross-Cultural Design. - Cham : Springer Berlin/Heidelberg. - 9783319579306 - 9783319579313 ; , s. 634-646
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Konferensbidrag (refereegranskat)abstract
- The development and advancement of ICT enable people to share excess capacity (e.g., car, apartment). In this paper, we focus on Didi Chuxing, which is one of the most prominent examples of car-sharing services in the sharing economy in China. This study aims to investigate the role of trust with car-sharing services in sharing economy from the consumers’ perspective. Based on the literature review, a research model with eight research hypotheses is proposed. The research model is empirically tested with Didi Chuxing by using survey data collected from a sample of 309 subjects. Six research hypotheses are significant supported, while two research hypotheses are rejected in this study. The results indicate that the most important determinant for the consumers’ trust in the car-sharing service platform is platform reputation. In addition, increased degree of the consumers’ familiarity with the car-sharing service platform has a positive impact the consumers’ trust in the car-sharing service platform. However, the perceived car-sharing service platform reputation has a positive impact on the consumers’ trust in drivers on the platform.
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| 27. |
- Gao, Shang, 1982-, et al.
(författare)
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Understanding college student' acceptance of online credit offering services in China
- 2016
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Ingår i: Proceedings of The Sixteenth International Conference on Electronic Business. - : CEUR-WS. ; , s. 673-678
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Konferensbidrag (refereegranskat)abstract
- With the rapid economic growth in China, peoples' consumption behavior is constantly changing. The online credit offering service is playing a more and more important role in China. In this paper, we aim to understand college students' acceptance of online credit offering services in China. A research model based on technology acceptance model (TAM) with six research hypotheses is proposed. And an empirical study with 239 subjects was conducted to test this model. According to the results, 4 of 6 hypotheses were supported. The results indicated that both perceived usefulness and subjective norm directly affected college students' behavior intention to use online credit offering services significantly.
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| 28. |
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| 29. |
- Han, Jing, et al.
(författare)
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Role of inflammation in the process of clinical Kashin-Beck disease : latest findings and interpretations
- 2015
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Ingår i: Inflammation Research. - : Springer. - 1023-3830 .- 1420-908X. ; 64:11, s. 853-860
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Tidskriftsartikel (refereegranskat)abstract
- Kashin-Beck disease (KBD), a particular type of osteoarthritis (OA), and an endemic disease with articular cartilage damage and chondrocytes apoptosis, can affect many joints, and the most commonly affected joints are the knee, ankle, and hand. KBD has traditionally been classified as a non-inflammatory OA. However, recent studies have shown that inflammation has played an important role in the development of KBD. Nowadays, clinical KBD is not only an endemic disease, but also a combined result of many other non-endemic factors, which contains age, altered biomechanics, joint trauma and secondary OA. The characteristics of the developmental joint failure of advanced KBD, because of the biochemical and mechanical processes, are tightly linked with the interaction of joint damage and its immune response, as well as the subsequent state of chronic inflammation leading to KBD progression. In this review, we focus on the epidemiology, pathology, imaging, cytokines and transduction pathways investigating the association of inflammation with KBD; meanwhile, a wide range of data will be discussed to elicit our current hypotheses considering the role of inflammation and immune activation in KBD development.
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| 30. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 31. |
- Kristan, Matej, et al.
(författare)
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The Sixth Visual Object Tracking VOT2018 Challenge Results
- 2019
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Ingår i: Computer Vision – ECCV 2018 Workshops. - Cham : Springer Publishing Company. - 9783030110086 - 9783030110093 ; , s. 3-53
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2018 is the sixth annual tracker benchmarking activity organized by the VOT initiative. Results of over eighty trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis and a “real-time” experiment simulating a situation where a tracker processes images as if provided by a continuously running sensor. A long-term tracking subchallenge has been introduced to the set of standard VOT sub-challenges. The new subchallenge focuses on long-term tracking properties, namely coping with target disappearance and reappearance. A new dataset has been compiled and a performance evaluation methodology that focuses on long-term tracking capabilities has been adopted. The VOT toolkit has been updated to support both standard short-term and the new long-term tracking subchallenges. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website (http://votchallenge.net).
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| 32. |
- Kristanl, Matej, et al.
(författare)
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The Seventh Visual Object Tracking VOT2019 Challenge Results
- 2019
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Ingår i: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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| 33. |
- Lin, Yuze, et al.
(författare)
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Balanced Partnership between Donor and Acceptor Components in Nonfullerene Organic Solar Cells with > 12% Efficiency
- 2018
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Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 30:16
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Tidskriftsartikel (refereegranskat)abstract
- Relative to electron donors for bulk heterojunction organic solar cells (OSCs), electron acceptors that absorb strongly in the visible and even near-infrared region are less well developed, which hinders the further development of OSCs. Fullerenes as traditional electron acceptors have relatively weak visible absorption and limited electronic tunability, which constrains the optical and electronic properties required of the donor. Here, high-performance fullerene-free OSCs based on a combination of a medium-bandgap polymer donor (FTAZ) and a narrow-bandgap nonfullerene acceptor (IDIC), which exhibit complementary absorption, matched energy levels, and blend with pure phases on the exciton diffusion length scale, are reported. The single-junction OSCs based on the FTAZ:IDIC blend exhibit power conversion efficiencies up to 12.5% with a certified value of 12.14%. Transient absorption spectroscopy reveals that exciting either the donor or the acceptor component efficiently generates mobile charges, which do not suffer from recombination to triplet states. Balancing photocurrent generation between the donor and nonfullerene acceptor removes undesirable constraints on the donor imposed by fullerene derivatives, opening a new avenue toward even higher efficiency for OSCs.
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| 34. |
- Liu, Jing, et al.
(författare)
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Fast charge separation in a non-fullerene organic solar cell with a small driving force
- 2016
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Ingår i: NATURE ENERGY. - : NATURE PUBLISHING GROUP. - 2058-7546. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Fast and efficient charge separation is essential to achieve high power conversion efficiency in organic solar cells (OSCs). In state-of-the-art OSCs, this is usually achieved by a significant driving force, defined as the offset between the bandgap (E-gap) of the donor/acceptor materials and the energy of the charge transfer (CT) state (E-CT), which is typically greater than 0.3 eV. The large driving force causes a relatively large voltage loss that hinders performance. Here, we report non-fullerene OSCs that exhibit ultrafast and efficient charge separation despite a negligible driving force, as E-CT is nearly identical to E-gap. Moreover, the small driving force is found to have minimal detrimental effects on charge transfer dynamics of the OSCs. We demonstrate a non-fullerene OSC with 9.5% efficiency and nearly 90% internal quantum efficiency despite a low voltage loss of 0.61V. This creates a path towards highly efficient OSCs with a low voltage loss.
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| 35. |
- Liu, Xiao-yan, et al.
(författare)
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Anti-ageing and antioxidant effects of sulfate oligosaccharides from green algae Ulva lactuca and Enteromorpha prolifera in SAMP8 mice
- 2019
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Ingår i: International Journal of Biological Macromolecules. - : ELSEVIER. - 0141-8130 .- 1879-0003. ; 139, s. 342-351
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Tidskriftsartikel (refereegranskat)abstract
- Oligosaccharides from green algae Ulva lactuca (ULO) and Enteromorpha prolifera (EPO) were used for investigation of anti-ageing effects and the underlying mechanism in SAMP8 mice. The structural properties of ULO and EPO were analyzed by fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry, and agarose gel electrophoresis. These oligosaccharides enhanced the glutathione, superoxide dismutase, catalase, and telomerase levels and total antioxidant capicity, and decreased the levels of malondialdehyde and advanced glycation end products. After ULO and EPO treatment, the levels of inflammatory factors, including IFN-gamma, TNF-alpha, and IL-6, decreased; the BDNF and ChAT levels increased; and hippocampal neurons were protected. Downregulation of the p53 and FOXO1 genes and upregulation of the Sirt1 gene indicated that ULO and EPO have potential therapeutic effects in the prevention of ageing in SAMP8 mice. By 16S rRNA gene high-throughput sequencing, the abundance of Desulfovibrio was discovered to be markedly different in mice treated with ULO and EPO. The abundances of Verrucomicrobiaceae, Odoribacteraceae, Mogibacteriaceae, Planococcaceae, and Coriobacteriaceae were positively correlated with age-related indicators. These results demonstrated that oligosaccharides from U. lactuca and E. prolifera are ideal candidate compounds that can be used in functional foods and pharmaceuticals to prevent ageing.
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| 36. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 37. |
- McAleese, Kirsty E., et al.
(författare)
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Post-mortem assessment in vascular dementia : advances and aspirations
- 2016
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease. Discussion: Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue. Conclusion: Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.
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| 38. |
- Merino, Jordi, et al.
(författare)
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Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium
- 2019
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 24:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10−6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.
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| 39. |
- Miao, Yanfeng, et al.
(författare)
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Stable and bright formamidinium-based perovskite light-emitting diodes with high energy conversion efficiency
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Solution-processable perovskites show highly emissive and good charge transport, making them attractive for low-cost light-emitting diodes (LEDs) with high energy conversion efficiencies. Despite recent advances in device efficiency, the stability of perovskite LEDs is still a major obstacle. Here, we demonstrate stable and bright perovskite LEDs with high energy conversion efficiencies by optimizing formamidinium lead iodide films. Our LEDs show an energy conversion efficiency of 10.7%, and an external quantum efficiency of 14.2% without outcoupling enhancement through controlling the concentration of the precursor solutions. The device shows low efficiency droop, i.e. 8.3% energy conversion efficiency and 14.0% external quantum efficiency at a current density of 300 mA cm(-2), making the device more efficient than state-of-the-art organic and quantum-dot LEDs at high current densities. Furthermore, the half-lifetime of device with benzylamine treatment is 23.7 hr under a current density of 100 mA cm(-2), comparable to the lifetime of near-infrared organic LEDs.
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| 40. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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| 41. |
- Sun, Wei, et al.
(författare)
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Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in Flavonoid Biosynthetic Pathway
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Chalcone synthase (CHS) catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1) encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants.
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| 42. |
- Ta, Huy Q., et al.
(författare)
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Single Cr atom catalytic growth of graphene
- 2018
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Ingår i: Nano Reseach. - : TSINGHUA UNIV PRESS. - 1998-0124 .- 1998-0000. ; 11:5, s. 2405-2411
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Tidskriftsartikel (refereegranskat)abstract
- Single atoms are the ultimate minimum size limit for catalysts. Graphene, as an exciting, ultimately thin (one atom thick) material can be imaged in a transmission electron microscope with relatively few imaging artefacts. Here, we directly observe the behavior of single Cr atoms in graphene mono- and di-vacancies and, more importantly, at graphene edges. Similar studies at graphene edges with other elemental atoms, with the exception of Fe, show catalytic etching of graphene. Fe atoms have been shown to both etch and grow graphene. In contrast, Cr atoms are only observed to induce graphene growth. Complementary theoretical calculations illuminate the differences between Fe and Cr, and confirm single Cr atoms as superior catalysts for sp(2) carbon growth.
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| 43. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 44. |
- Xu, Jianhua, et al.
(författare)
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A Variant of the Autophagy-Related 5 Gene is Associated with Child Cerebral Palsy
- 2017
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral palsy (CP) is a major cause of childhood disability in developed and developing countries, but the pathogenic mechanisms of CP development remain largely unknown. Autophagy is a highly conserved cellular self-digestion of damaged organelles and dysfunctional macromolecules. Growing evidence suggests that autophagy-related gene 5 (ATG5)-dependent autophagy is involved in neural development, neuronal differentiation, and neurological degenerative diseases. The aim of this study was to analyze ATG5 protein expression and gene polymorphisms in Chinese patients with CP and to evaluate the importance of ATG5 in the development of CP. Five polymorphisms from different regions of the ATG5 gene (rs510432, rs3804338, rs573775, rs2299863, and rs6568431) were analyzed in 715 CP patients and 658 controls using MassARRAY. Of these, 58 patients and 56 controls were selected for measurement of plasma ATG5 level using ELISA. The relevance of disease-associated SNPs was evaluated using the SHEsis program. We identified a significant association between rs6568431 and CP (OR = 1.388, 95% CI = 1.173∼1.643, Pallele = 0.0005, Pgenotype = 0.0015). Subgroup analysis showed a highly significant association of rs6568431 with spastic CP (n = 468, OR = 1.511, 95% CI = 1.251∼1.824, Pallele = 8.50e−005, Pgenotype = 1.57e−004) and spastic quadriplegia (OR = 1.927, 95% CI = 1.533∼2.421, Pallele = 7.35e−008, Pgenotype = 3.24e−009). Furthermore, mean plasma ATG5 levels were lower in CP patients than in controls, and individuals carrying the AA genotype of rs6568431 that was positively associated with CP had lower plasma ATG5 levels (P < 0.05). This study demonstrated an association of an ATG5 gene variant and low level of ATG5 protein with CP, and stronger associations with severe clinical manifestations were identified. Our results provide novel evidence for a role of ATG5 in CP and shed light on the molecular mechanisms underlying this neurodevelopmental disorder.
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