| 1. |
- Bai, Yang, et al.
(författare)
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Geometry design of tethered small-molecule acceptor enables highly stable and efficient polymer solar cells
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- With the power conversion efficiency of binary polymer solar cells dramatically improved, the thermal stability of the small-molecule acceptors raised the main concerns on the device operating stability. Here, to address this issue, thiophene-dicarboxylate spacer tethered small-molecule acceptors are designed, and their molecular geometries are further regulated via the thiophene-core isomerism engineering, affording dimeric TDY-alpha with a 2, 5-substitution and TDY-beta with 3, 4-substitution on the core. It shows that TDY-alpha processes a higher glass transition temperature, better crystallinity relative to its individual small-molecule acceptor segment and isomeric counterpart of TDY-beta, and amore stablemorphology with the polymer donor. As a result, the TDY-alpha based device delivers a higher device efficiency of 18.1%, and most important, achieves an extrapolated lifetime of about 35000 hours that retaining 80% of their initial efficiency. Our result suggests that with proper geometry design, the tethered small-molecule acceptors can achieve both high device efficiency and operating stability.
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| 2. |
- Pan, Qinying, et al.
(författare)
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Ultrafast charge transfer dynamics in 2D covalent organic frameworks/Re-complex hybrid photocatalyst
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Rhenium(I)-carbonyl-diimine complexes have emerged as promising photocatalysts for carbon dioxide reduction with covalent organic frameworks recognized as perfect sensitizers and scaffold support. Such Re complexes/covalent organic frameworks hybrid catalysts have demonstrated high carbon dioxide reduction activities but with strong excitation energy-dependence. In this paper, we rationalize this behavior by the excitation energy-dependent pathways of internal photo-induced charge transfer studied via transient optical spectroscopies and time-dependent density-functional theory calculation. Under band-edge excitation, the excited electrons are quickly injected from covalent organic frameworks moiety into catalytic RheniumI center within picosecond but followed by fast backward geminate recombination. While under excitation with high-energy photon, the injected electrons are located at high-energy levels in RheniumI centers with longer lifetime. Besides those injected electrons to RheniumI center, there still remain some long-lived electrons in covalent organic frameworks moiety which is transferred back from RheniumI. This facilitates the two-electron reaction of carbon dioxide conversion to carbon monoxide.
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| 3. |
- Demerath, Ellen W., et al.
(författare)
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Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:15, s. 4464-4479
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 x 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.
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| 4. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 5. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:8, s. 753-60
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
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| 9. |
- Kong, Yi, et al.
(författare)
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Elastic and thermodynamic properties of the Ni-B system studied by first-principles calculations and experimental measurements
- 2010
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Ingår i: Calphad. - : Elsevier BV. - 0364-5916 .- 1873-2984. ; 34:2, s. 245-251
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Tidskriftsartikel (refereegranskat)abstract
- The elastic and thermodynamic properties of NiB, Ni2B, Ni3B, orthorhombic Ni4B3(O-Ni4B3), monoclinic Ni4B3(M-Ni4B3), and Ni23B6, are calculated via first-principles method for the Ni-B system. The ground state energies, the full sets of elastic constants and the associated macroscopic elastic parameters of these Ni-B alloys are computed for the first time. Taking contributions from lattice vibrations and thermally excited electrons into account, thermodynamic properties at finite temperatures are then predicted. In addition, we measure the molar heat capacity at constant pressure for NiB and compare the results with the theoretical predictions. Various calculations demonstrate that the first-principles calculation can be used to clarify the diverse experimental data, and provide reliable thermodynamic data. (C) 2010 Elsevier Ltd. All rights reserved.
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| 10. |
- Li, Junhao, 1989-, et al.
(författare)
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Dissecting the Structural Plasticity and Dynamics of Cytochrome P450 2B4 by Molecular Dynamics Simulations
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The plasticity of cytochrome P450 enzymes (P450s) is known to contribute significantly to their catalytic capacity of metabolizing various substrates. Although numerous studies have been performed, factors governing the plasticity and dynamics of P450s are still not fully understood. In this study, taking CYP2B4 as an example, we dissect the protein plasticity and dynamics in different environments. CYP2B4 is featured by a high degree of plasticity that exhibits open, closed, and intermediate states. By analyzing the CYP2B4 crystal structures, we identified the structural features for the closed, open and intermediate states. Interestingly, formation of the dimer structure was found in the open and intermediate structures. The subsequent MD simulations of the open structure in water confirmed the importance of the dimer form in stabilizing the open conformations. MD simulations of the closed and open structures in the membrane environment and the free energies for opening the F-G cassette obtained from the umbrella sampling calculations indicate that the membrane environment is important for stabilizing the F-G cassette. The dynamical network analysis indicates that Asp105 on the B-C loop plays an important role in transiting the structure from the open to intermediate. Our results thus unveil the mechanism of dimer formation and open-to-intermediate transition for CYP2B4 in the water and membrane environments.
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| 11. |
- Li, Junhao, et al.
(författare)
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Dissecting the Structural Plasticity and Dynamics of Cytochrome P450 2B4 by Molecular Dynamics Simulations
- 2020
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 60:10, s. 5026-5035
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Tidskriftsartikel (refereegranskat)abstract
- The plasticity of cytochromes P450 (P450s) is known to contribute significantly to their catalytic capacity of metabolizing various substrates. Although numerous studies have been performed, factors governing the plasticity and dynamics of P450s are still not fully understood. In this study, taking CYP2B4 as an example, we dissect the protein plasticity and dynamics in different environments. CYP2B4 is featured by a high degree of plasticity, which exhibits open, closed, and intermediate states. By analyzing the CYP2B4 crystal structures, we identified the structural features for the closed, open, and intermediate states. Interestingly, formation of the dimer structure was found in the open and intermediate states. The subsequent molecular dynamics (MD) simulations of the open structure in water confirmed the importance of the dimer form in stabilizing the open conformations. MD simulations of the closed and open structures in the membrane environment and the free energies for opening the F-G cassette obtained from the umbrella sampling calculations indicate that the membrane environment is important for stabilizing the F-G cassette. The dynamical network analysis indicates that Asp105 on the B-C loop plays an important role in transiting the structure from the open to the intermediate state. Our results thus unveil the mechanisms of dimer formation and open-to-intermediate transition for CYP2B4 in the water and membrane environments.
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| 12. |
- Lin, Xihong, et al.
(författare)
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Effect of alloying on the dynamics of coherent acoustic phonons in bismuth double perovskite single crystals
- 2021
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Ingår i: Optics Express. - : Optical Society of America. - 1094-4087. ; 29:5, s. 7948-7955
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Tidskriftsartikel (refereegranskat)abstract
- The bismuth double perovskite Cs2AgBiBr6 has been regarded as a potential candidate for lead-free perovskite photovoltaics. A detailed study on the coherent acoustic phonon dynamics in the pure, Sb- and T1-alloyed Cs2AgBiBr6 single crystals is performed to understand the effects of alloying on the phonon dynamics and band edge characteristics. The coherent acoustic phonon frequencies are found to be independent of the alloying, while the damping rates are highly dependent on the alloying. Based on the mechanism of coherent acoustic phonon damping, a technique has been successfully developed that can accurately extract the absorption spectra near the indirect band gap for these single crystals with coefficients on the order of 10(2) cm(-1). (C) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
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| 13. |
- Lin, Xin (Maxwell), et al.
(författare)
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Smart coordinated multi-energy intra-scheduling inter-sharing and cost-saving redistribution for multiple microgrids
- 2023
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Ingår i: Sustainable cities and society. - : ELSEVIER. - 2210-6707. ; 97
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Tidskriftsartikel (refereegranskat)abstract
- Sustainable and clean multi-energy systems have been hybrid coordinated in microgrid (MG) to fulfill regional multi-energy users economically, but shortages and surpluses still exist. The growth of win-win energy sharing between MGs attracts attention to smart information center (SIC) concept in MGs community, which facilitates sustainable solutions across three key objectives: lower carbon emission, sufficient utilization, and long-term cooperation. This paper designs a two-stage decision framework for day-ahead operations of SIC, where the first stage minimizes the total cost (i.e. operational cost and carbon emission cost) by the proposed multi-energy intra-scheduling and inter-sharing model (MIIM) and the second stage implements the smart cost-saving redistribution model (SCRM) to stimulate MGs in long-term joining of energy sharing. The extended alternating direction multipliers method algorithm (E-ADMM) is developed to protect the privacy of MGs data while approximating the optimal solution of MIIM. The case study proves that a) demand response and energy sharing in MIIM result in cost savings of 2.01% for carbon emissions and 7.25% for total operations; b) renewable energy has been fully utilized and the total multi-energy loss has been avoided nearly 92.22% in MIIM; c) the asymmetric Nash bargaining approach fits the SCRM with incentive cooperation, whereby those who contribute more gain a higher share; d) the optimal gap of E-ADMM is less than 0.2% by iterated insensitive decision result from each MG, which computes in polynomial time when the scale of MG increases; e) the two-stage framework performs better with more heterogeneity of MGs. Furthermore, we provide valuable insights for guidance and models with worldwide generalization potential.
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| 14. |
- Liu, Weihua, et al.
(författare)
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Modeling of Threshold Voltage Distribution in 3D NAND Flash Memory
- 2021
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Ingår i: PROCEEDINGS OF THE 2021 DESIGN, AUTOMATION & TEST IN EUROPE CONFERENCE & EXHIBITION (DATE 2021). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 1729-1732
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Konferensbidrag (refereegranskat)abstract
- 3D NAND flash memory faces unprecedented complicated interference than planar NAND flash memory, resulting in more concern regarding reliability and performance. Stronger error correction code (ECC) and adaptive reading strategies are proposed to improve the reliability and performance taking a threshold voltage (Vth) distribution model as the backbone. However, the existing modeling methods are challenged to develop such a Vth distribution model for 3D NAND flash memory. To facilitate it, in this paper, we propose a machine learning-based modeling method. It employs a neural network taking advantage of the existing modeling methods and fully considers multiple interferences and variations in 3D NAND flash memory. Compared with state-of-the-art models, evaluations demonstrate it is more accurate and efficient for predicting Vth distribution.
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| 15. |
- Liu, Weihua, et al.
(författare)
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Pricing decision with conspicuous customers: quick responses versus value-added services
- 2021
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Ingår i: International Journal of Production Research. - : TAYLOR & FRANCIS LTD. - 0020-7543 .- 1366-588X. ; 59:6, s. 1691-1713
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Tidskriftsartikel (refereegranskat)abstract
- In order to eliminate the negative effects of customer strategic behaviour, retailers often adopt quick response or value-added services. While in a luxury market with conspicuous customers, retailers pricing decisions of these two strategies become more complicated. This paper studies a supply chain with a retailer serving a mixture of conspicuous and ordinary strategic customers. We develop three models so that the retailer provides (i) neither quick response nor value-added services; (ii) only quick response; (iii) only value-added services. Subsequently, we analyse the impacts of conspicuous customers on quick response and value-added services by pricing and strategy comparisons. The model further extends to the situation including both strategies. The results show that, firstly, when the proportion is less than a threshold, the retailer should adopt a low price strategy, and vice versa. Besides, the quick response could induce the retailer to adopt high price while value-added services inhibit it. Secondly, the customer conspicuous behaviour can motivate retailers to provide quick response and inhibit their value-added services. Finally, by observing the retailers decisions when they can adopt two strategies simultaneously, we find that the existence of quick response can amplify the benefits of value-added services.
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| 16. |
- Liu, Yang, et al.
(författare)
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Defect State Assisted Z-scheme Charge Recombination in Bi2O2CO3/Graphene Quantum Dot Composites for Photocatalytic Oxidation of NO
- 2020
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Ingår i: ACS Applied Nano Materials. - : American Chemical Society (ACS). - 2574-0970. ; 3:1, s. 772-781
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we explored the photoinduced charge carriers dynamics rationalizing the photocatalytic oxidation of NO over N-doped Bi2O2CO3/graphene quantum dots composites(N-BOC/GQDs) via time-resolved photoluminescence (TRPL). Under visible light illumination, only GQDs can be photoexcited and inject electrons to N-BOC within 0.5 ns. Under UV light irradiation, the interfacial Z-scheme heterojunction recombination between the electrons in N-BOC and holes in GQDs dominate the depopulation of excited states within 0.36 ns. Such efficient Z-scheme recombination regardless of the large energy difference (1.66 eV) is mediated by the interfacial oxygen vacany defect states characterized by both density functional theory calculations (DFT) and electron paramagnetic resonance (EPR) measurement. This finding provide a novel strategic view to improve the photocatalytic performance of the nanocomposite by interfacial engineering
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| 17. |
- Liu, Yang, et al.
(författare)
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Inorganic ligands-mediated hole attraction and surface structuralreorganization in InP/ZnS QD photocatalysts studied via ultrafast visibleand midinfrared spectroscopies
- 2022
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Ingår i: SCIENCE CHINA Materials. - : Springer Science and Business Media LLC. - 2095-8226 .- 2199-4501. ; 65:9, s. 2529-2539
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Tidskriftsartikel (refereegranskat)abstract
- Photoinduced carrier dynamical processes dominate the optical excitation properties of photocatalysts and further determine the photocatalytic performance. In addition, as the electrons generally possess a faster transfer rate than holes, hole transfer and accumulation are critical, and they play the key efficiency-limiting step during the photocatalytic process. Therefore, a comprehensive understanding of the dynamics of photogenerated holes and their determining factors in the photocatalytic system is highly essential to rationalize the full catalytic mechanism and develop highly efficient photocatalysts, which have not yet been revealed. In this work, the photoinduced charge carrier dynamics in InP/ZnS quantum dots (QDs) capped with long-chain L-typed ligands (oleylamine) and inorganic ligands (sulfide ion (S2−)) were explored. Time-resolved photoluminescence and femtosecond transient-absorption spectroscopy unambiguously confirmed the ultrafast hole transfer from the InP core to S2− ligands. Moreover, by probing the bleach of vibrational stretching of the ligands with transient midinfrared absorption spectroscopy, the hole transfer time was determined to be 4.2 ps. The injected holes are long-lived at the S2− ligands (>4.5 ns), and they can remove electrostatically attached surfactants to compensate for the spatial charge redistribution. Finally, compared with other inorganic ligands such as Cl− and PO43−, S2− balances the ionic radii and net charge to ensure the optimal condition for charge transfer. Such observation rationalizes the excellent photocatalytic H2 evolution (213.6 µmol mg−1 within 10 h) in InP/ZnS QDs capped with S2− compared with those capped with other ligands and elucidates the role of surface ligands in the photocatalytic activity of colloidal QDs.
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| 18. |
- 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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| 19. |
- Qian, Frank, et al.
(författare)
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n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes : An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:5, s. 1133-1142
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.RESEARCH DESIGN AND METHODS For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a pre-specified protocol, and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.RESULTS A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.CONCLUSIONS Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.
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| 20. |
- 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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| 21. |
- 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
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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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| 22. |
- Wu, Bo, et al.
(författare)
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Strong self-trapping by deformation potential limits photovoltaic performance in bismuth double perovskite
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Bismuth-based double perovskite Cs2AgBiBr6 is regarded as a potential candidate for low-toxicity, high-stability perovskite solar cells. However, its performance is far from satisfactory. Albeit being an indirect bandgap semiconductor, we observe bright emission with large bimolecular recombination coefficient (reaching 4.5 +/- 0.1 x 10(-11) cm(3) s(-1)) and low charge carrier mobility (around 0.05 cm(2) s(-1) V-1). Besides intermediate Frohlich couplings present in both Pb-based perovskites and Cs2AgBiBr6, we uncover evidence of strong deformation potential by acoustic phonons in the latter through transient reflection, time-resolved terahertz measurements, and density functional theory calculations. The Frohlich and deformation potentials synergistically lead to ultrafast self-trapping of free carriers forming polarons highly localized on a few units of the lattice within a few picoseconds, which also breaks down the electronic band picture, leading to efficient radiative recombination. The strong self-trapping in Cs2AgBiBr6 could impose intrinsic limitations for its application in photovoltaics.
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| 23. |
- Zhao, Qian, et al.
(författare)
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Size-Dependent Multi-Electron Donation in Metal-Complex Quantum Dots Hybrid Catalyst for Photocatalytic Carbon Dioxide Reduction
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Ingår i: Advanced Functional Materials. - 1616-301X.
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Tidskriftsartikel (refereegranskat)abstract
- The effective conversion of carbon dioxide (CO2) into valuable chemical fuels relies significantly on the donation of multiple electrons. Its efficiency is closely linked to both the density and lifetime of excited charge carriers. In this study, a hybrid catalyst system comprising covalently bonded InP/ZnS quantum dots (QDs) and Re-complexes is showcased. The electronic band alignment between the QDs and the Re-complexes is revealed to dominate the multi-electron transfer process for photocatalytic conversion to methane (CH4). Notably, the size of the QDs is found to be a determining parameter. Among the three QD sizes investigated, transient absorption spectroscopy studies unveil that rapid multi-electron transfer from the QDs to the Re-catalyst occurs in smaller QDs (2.3 nm) due to the substantial driving force. Consequently, the photocatalytic conversion of CO2 to CH4 is significantly enhanced with a turnover number of 6, corresponding to the overall apparent quantum yield of ≈1%. This research underscores the possibilities of engineering multi-electron transfer by manipulating the electronic band alignment within a catalytic system. This can serve as a guide for optimizing photocatalytic CO2 reduction.
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| 24. |
- Zhou, Weihua, et al.
(författare)
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Purine metabolism regulates DNA repair and therapy resistance in glioblastoma
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guanylates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, administration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.
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| 25. |
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