| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Ablikim, M., et al.
(författare)
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Observation of the decay psi(3686) -> Lambda(Sigma)over-bar(+/-) pi(-/+) + c.c
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112007-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1:06 X 10(8) psi(3686) events collected with the BESIII detector, we present the first observation of the decays of psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c. and psi(3686) -> Lambda(Sigma) over bar (-) pi(+) + c.c. The branching fractions are measured to be B(psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c.) = (1.40 +/- 0.03 +/- 0.13) X 10(-4) and B(psi(3686) -> Lambda (Sigma) over bar (-) pi(+) + c.c.) = (1.54 +/- 0.04 +/- 0.13) X 10(-4) where the first errors are statistical and the second ones systematic.
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| 5. |
- Ablikim, M., et al.
(författare)
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Search for eta(c)(2S)h(c) -> p(p)over-bar decays and measurements of the chi(cJ) -> p(p)over-bar branching fractions
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112001-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1.06 x 10(8)psi(3686) events collected with the BESIII detector at BEPCII, the decays eta(c)(2S) -> p (p) over bar and h(c) -> p (p) over bar are searched for, where eta(c)(2S) and h(c) are reconstructed in the decay chains psi(3686) -> gamma eta(c)(2S), eta(c)(2S) -> p (p) over bar and psi(3686) -> pi(0)h(c), h(c) -> p (p) over bar, respectively. No significant signals are observed. The upper limits of the product branching fractions are determined to be B(psi(3686) -> gamma eta(c)(2S)) x B(eta(c)(2S) -> p (p) over bar) < 1.4 x 10(-6) and B(psi(3686) -> pi(0)h(c)) x B(h(c) -> p<(p)over bar>) < 1.3 x 10(-7) at the 90% C.L.. The branching fractions for chi(cJ) -> p<(p)over bar> (J = 0, 1, 2) are also measured to be (24.5 +/- 0.8 +/- 1.3, 8.6 +/- 0.5 +/- 0.5, 8.4 +/- 0.5 +/- 0.5) x 10(-5), which are the world's most precise measurements.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- 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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| 10. |
- Fan, Chuan-Wen, et al.
(författare)
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Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
- 2020
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Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear.Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC.Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.
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| 11. |
- 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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| 12. |
- 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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| 13. |
- Lu, Yingchang, et al.
(författare)
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Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:2, s. 477-486
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Tidskriftsartikel (refereegranskat)abstract
- Background: Risk variants identified so far for colorectal cancer explain only a small proportion of milial risk of this cancer, particularly in Asians.Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, cluding 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 omising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls European descent. To identify additional risk variants in known colorectal cancer loci, we performed nditional analyses in East Asians.Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk P = 3.9 x 10(-8) in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This sociation was replicated in European descendants using a variant (rs2938616) in complete linkage sequilibrium with rs67052019 (P = 7.7 x 10(-3)). Of the remaining 59 variants, 12 showed an association P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 x 10(-8) and o variants with an association near the genome-wide significance level (rs60911071, P = 5.8 x 10(-8); 62558833, P = 7.5 x 10(-8)) in the combined analyses of Asian- and European-ancestry data. In addition, ing data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS.Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for lorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the iology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal ncer risk loci identified previously.Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal ncer risk.
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| 14. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 15. |
- Ning, Haoran, et al.
(författare)
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Two-Dimensional and Subnanometer-Thin Quasi-Copper-Sulfide Semiconductor Formed upon Copper-Copper Bonding
- 2021
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:1, s. 873-883
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Tidskriftsartikel (refereegranskat)abstract
- Ultrathin two-dimensional (2D) semiconductors exhibit outstanding properties, but it remains challenging to obtain monolayer-structured inorganic semiconductors naturally occurring as nonlayered crystals. Copper sulfides are a class of widely studied nonlayered metal chalcogenide semiconductors. Although 2D copper sulfides can provide extraordinary physical and chemical applications, investigations of 2D copper sulfides in the extreme quantum limit are constrained by the difficulty in preparing monolayered copper sulfides. Here, we report a subnanometer-thin quasi-copper-sulfide (q-CS) semiconductor formed upon self-assembly of copper(I)-dodecanethiol complexes. Extended X-ray absorption fine structure analysis revealed that the existence of Cu-Cu bonding endowed the layer-structured q-CS with semiconductor properties, such as appreciable interband photoluminescence. Theoretical studies on the band structure demonstrated that the optical properties of copper-dodecanethiol assemblies were dominated by the q-CS layer and the photoluminescence originated from exciton radiative recombination across an indirect band gap, borne out by experimental observation at higher temperatures, but with the onset of a direct emission process at cryogenic temperatures. The following studies revealed that the metal-metal bonding occurred not only in copper-alkanethiolate complex assemblies with variable alkyl chain length but also in silver-alkanethiolate and cadmium-alkanethiolate assemblies. Therefore, the current studies may herald a class of 2D semiconductors with extremely thin thickness out of nonlayered metal sulfides to bridge the gap between conventional inorganic semiconductors and organic semiconductors.
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| 16. |
- 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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| 17. |
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| 18. |
- 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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| 19. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 20. |
- 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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| 21. |
- Wu, Jing, et al.
(författare)
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Interleukin-33 is a Novel Immunosuppressor that Protects Cancer Cells from TIL Killing by a Macrophage-Mediated Shedding Mechanism
- 2021
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Ingår i: Advanced Science. - : Wiley. - 2198-3844. ; 8:21
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Tidskriftsartikel (refereegranskat)abstract
- Recognition of specific antigens expressed in cancer cells is the initial process of cytolytic T cell-mediated cancer killing. However, this process can be affected by other non-cancerous cellular components in the tumor microenvironment. Here, it is shown that interleukin-33 (IL-33)-activated macrophages protect melanoma cells from tumor-infiltrating lymphocyte-mediated killing. Mechanistically, IL-33 markedly upregulates metalloprotease 9 (MMP-9) expression in macrophages, which acts as a sheddase to trim NKG2D, an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, subsets of CD4+ T cells, iNKT cells, and gamma delta T cells. Further, MMP-9 also cleaves the MHC class I molecule, cell surface antigen-presenting complex molecules, expressed in melanoma cells. Consequently, IL-33-induced macrophage MMP-9 robustly mitigates the tumor killing-effect by T cells. Genetic and pharmacological loss-of-function of MMP-9 sheddase restore T cell-mediated cancer killing. Together, these data provide compelling in vitro and in vivo evidence showing novel mechanisms underlying the IL-33-macrophage-MMP-9 axis-mediated immune tolerance against cancer cells. Targeting each of these signaling components, including IL-33 and MMP-9 provides a new therapeutic paradigm for improving anticancer efficacy by immune therapy.
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| 22. |
- Zhang, Huai, et al.
(författare)
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A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
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Ingår i: Hepatology international. - 1936-0541.
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Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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| 23. |
- 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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| 24. |
- Zhou, Weibin, et al.
(författare)
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Targeting VEGF-A/VEGFR2 Y949 Signaling-Mediated Vascular Permeability Alleviates Hypoxic Pulmonary Hypertension
- 2022
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 146:24, s. 1855-1881
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Tidskriftsartikel (refereegranskat)abstract
- Background:Pulmonary hypertension (PH) is associated with increased expression of VEGF-A (vascular endothelial growth factor A) and its receptor, VEGFR2 (vascular endothelial growth factor 2), but whether and how activation of VEGF-A signal participates in the pathogenesis of PH is unclear. Methods:VEGF-A/VEGFR2 signal activation and VEGFR2 Y949-dependent vascular leak were investigated in lung samples from patients with PH and mice exposed to hypoxia. To study their mechanistic roles in hypoxic PH, we examined right ventricle systolic pressure, right ventricular hypertrophy, and pulmonary vasculopathy in mutant mice carrying knock-in of phenylalanine that replaced the tyrosine at residual 949 of VEGFR2 (Vefgr2(Y949F)) and mice with conditional endothelial deletion of Vegfr2 after chronic hypoxia exposure. Results:We show that PH leads to excessive pulmonary vascular leak in both patients and hypoxic mice, and this is because of an overactivated VEGF-A/VEGFR2 Y949 signaling axis. In the context of hypoxic PH, activation of Yes1 and c-Src and subsequent VE-cadherin phosphorylation in endothelial cells are involved in VEGFR2 Y949-induced vascular permeability. Abolishing VEGFR2 Y949 signaling by Vefgr2(Y949F) point mutation was sufficient to prevent pulmonary vascular permeability and inhibit macrophage infiltration and Rac1 activation in smooth muscle cells under hypoxia exposure, thereby leading to alleviated PH manifestations, including muscularization of distal pulmonary arterioles, elevated right ventricle systolic pressure, and right ventricular hypertrophy. It is important that we found that VEGFR2 Y949 signaling in myeloid cells including macrophages was trivial and dispensable for hypoxia-induced vascular abnormalities and PH. In contrast with selective blockage of VEGFR2 Y949 signaling, disruption of the entire VEGFR2 signaling by conditional endothelial deletion of Vegfr2 promotes the development of PH. Conclusions:Our results support the notion that VEGF-A/VEGFR2 Y949-dependent vascular permeability is an important determinant in the pathogenesis of PH and might serve as an attractive therapeutic target pathway for this disease.
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| 25. |
- 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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| 26. |
- Axelsson, Josefine, et al.
(författare)
-
A Precipitation Isotopic Response in 2014-2015 to Moisture Transport Changes in the Central Himalayas
- 2023
-
Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 128:13
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of moisture transport and sources on precipitation stable isotopes (d(18)O and d-excess) in the central Himalayas are crucial to understanding the climatic archives. However, this is still unclear due to the lack of in-situ observations. Here we present measurements of stable isotopes in precipitation at two stations (Yadong and Pali) in the central Himalayas during 2014-2015. Combined with simulations from the dispersion model FLEXPART, we investigate effects on precipitation stable isotopes related to changes in moisture sources and convections in the region, and possible influence by El Nino. Our results suggest that the moisture supplies related to evaporation over northeastern India and moisture losses related to convective activities over the Bay of Bengal (BoB) and Bangladesh region play important roles in changes in d(18)O and d-excess in precipitation in the Yadong Valley. Outgoing longwave radiation and moisture flux divergence analysis further confirm that the contribution from continental evaporation dominates the moisture supply in the central Himalayas with a lesser contribution from convection over the BoB during the 2015 monsoon season compared with 2014. A change in the altitude effect is observed in 2015, which is more significant than the temperature and precipitation amount effect during the observation period. These findings provide valuable insights into climatic interpretations of paleo-isotopic archives with an isotopic response to changes in moisture transport to the central Himalayas.
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| 27. |
- Burn, E., et al.
(författare)
-
Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19. Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.
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| 28. |
- Carlsson-Jonsson, Anna, et al.
(författare)
-
N-terminal truncations of substance P1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats
- 2014
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 738, s. 319-325
-
Tidskriftsartikel (refereegranskat)abstract
- Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess antinociceptive properties. We also studied the effects of intraperitoneal injection of an amidated analog of this heptapeptide and of its truncated analogs, all of which had high affinity to the SP1-7 binding site, to evaluate the importance of the removed amino acids for the bioclistribution and stability of the peptides. Most of the examined compounds alleviated mechanical alloclynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by arty of the compounds tested. Most of the amino acids in the heptapepticle structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapepticle and its N-Lerminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
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| 29. |
- Chen, Hualong, et al.
(författare)
-
Direct Observation of Photon Induced Giant Band Renormalization in 2D PdSe2 Dichalcogenide by Transient Absorption Spectroscopy
- 2023
-
Ingår i: Small. - : John Wiley & Sons. - 1613-6810 .- 1613-6829. ; 19:46
-
Tidskriftsartikel (refereegranskat)abstract
- Insight into fundamental light-matter interaction as well as underlying photo-physical processes is crucial for the development of novel optoelectronic devices. Palladium diselenide (PdSe2), an important representative of emerging 2D noble metal dichalcogenides, has gain considerable attention owing to its unique optical, physical, and chemical properties. In this study, 2D PdSe2 nanosheets (NSs) are prepared using the liquid-phase exfoliation method. A broadband carrier relaxation dynamics from visible to near-infrared bands are revealed using a time-resolved transient absorption spectrometer, giving results that indicate band filling and bandgap renormalization (BGR) effects in the 2D PdSe2 NSs. The observed blue-shift of the transient absorption spectra at the primary stage and the subsequent red-shift can be ascribed to this BGR effect. These findings reveal the many-body character of the 2D TMDs material and may hold keys for applications in the field of optoelectronics and ultrafast photonics.
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| 30. |
- Chen, Hong, et al.
(författare)
-
PKU-3 : An HCI-Inclusive Aluminoborate for Strecker Reaction Solved by Combining RED and PXRD
- 2015
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 137:22, s. 7047-7050
-
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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| 31. |
- Chen, Xuehan, et al.
(författare)
-
Perspective Phosphine oxide additives for perovskite diodes and solar cells
- 2023
-
Ingår i: Chem. - : CELL PRESS. - 2451-9308 .- 2451-9294. ; 9:3, s. 562-575
-
Forskningsöversikt (refereegranskat)abstract
- Lead halide perovskites have been considered promising semicon-ducting materials for next-generation optoelectronic devices due to their solution processability and excellent optoelectronic proper-ties. Device performance of perovskite light-emitting diodes (PeLEDs) and perovskite solar cells (PSCs) has been rapidly devel-oped during the past decade. Very recently, organic molecules containing phosphine oxide groups have emerged as promising ad-ditives and passivators to improve the device performance and sta-bility of both PeLEDs and PSCs. In this perspective, we summarize recent progress in the development of new phosphine-oxide-based additives for PeLEDs and PSCs. The passivation mechanism, molecule design principle, and structure-property relationship of phosphine oxide molecules for PeLEDs and PSCs are systematically discussed and analyzed. Finally, we provide an outlook on the mo-lecular design of novel phosphine oxide compounds for efficient and stable PeLEDs and PSCs in the future.
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| 32. |
- Cheng, Li-Peng, et al.
(författare)
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Efficient CsPbBr3 Perovskite Light-Emitting Diodes Enabled by Synergetic Morphology Control
- 2019
-
Ingår i: Advanced Optical Materials. - : WILEY-V C H VERLAG GMBH. - 2162-7568 .- 2195-1071. ; 7:4
-
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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| 33. |
- Cheng, Shi-Ping, et al.
(författare)
-
Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
- 2021
-
Ingår i: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
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| 34. |
- Cui, Yong, et al.
(författare)
-
Over 16% efficiency organic photovoltaic cells enabled by a chlorinated acceptor with increased open-circuit voltages
- 2019
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
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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| 35. |
- de Vries, Paul S., et al.
(författare)
-
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
-
Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
-
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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| 36. |
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| 37. |
- Ding, Jing, et al.
(författare)
-
Routing policy choice set generation in stochastic time-dependent networks : Case studies for Stockholm and Singapore
- 2014
-
Konferensbidrag (refereegranskat)abstract
- Transportation systems are inherently uncertain due to the occurrence of random disruptions; meanwhile, real-time traveler information offers the potential to help travelers make better route choices under such disruptions. This paper presents the first revealed preference (RP) study of routing policy choice where travelers opt for routing policies instead of fixed paths. 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. An efficient algorithm to find the optimal routing policy (ORP) in large-scale networks is presented, as the algorithm is a building block of any routing policy choice set generation method. Two case studies are conducted in Stockholm, Sweden and Singapore, respectively. Data for the underlying stochastic time-dependent network are generated from taxi Global Positioning System (GPS) traces through the methods of map-matching and non-parametric link travel time estimation. The routing policy choice sets are then generated by link elimination and simulation, in which the ORP algorithm is repetitively executed. The generated choice sets are first evaluated based on whether or not they include the observed GPS traces on a specific day, which is defined as coverage. They are then evaluated on the basis of adaptiveness, defined as the capability of a routing policy to be realized as different paths over different days. It is shown that using a combination of link elimination and simulation methods yield satisfactory coverage. The comparison to a path choice set benchmark suggests that a routing policy choice set could potentially provide better coverage and capture the adaptive nature of route choice. The routing policy choice set generation enables the development of a discrete choice model of routing policy choice, which will be explored in the second stage of the study.
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| 38. |
- Ding, Jing, et al.
(författare)
-
Routing Policy Choice Set Generation in Stochastic Time-Dependent Networks Case Studies for Stockholm, Sweden, and Singapore
- 2014
-
Ingår i: Transportation Research Record. - : SAGE Publications. - 0361-1981 .- 2169-4052. ; :2466, s. 76-86
-
Tidskriftsartikel (refereegranskat)abstract
- Transportation systems are inherently uncertain because of random disruptions; nevertheless, real-time information can help travelers make better route choices under such disruptions. The first revealed-preference study of routing policy choice is presented. A "routing policy" is defined as a decision rule applied at each link that maps possible realized traffic conditions to decisions to be made on the link next. The policy represents a traveler's ability to incorporate real-time information not yet available at the time of decision. Two case studies are conducted in Stockholm, Sweden, and in Singapore. Data for the underlying stochastic time-dependent network are generated from taxi GPS traces through map-matching and nonparametric link travel time estimation. An efficient algorithm to find the optimal touting policy in large-scale networks is first presented, which is a building block of any routing policy choice set generation method. The routing policy choice sets are then generated by link elimination and simulation. The generated choice sets are first evaluated on the basis of whether they include the observed traces on a specific day, or coverage. The sets are then evaluated on the basis of "adaptiveness," defined as the capability of a routing policy to be realized as different paths over different days. A combination of link elimination and simulation methods yields satisfactory coverage. The comparison with a path choice set benchmark also suggests that a routing policy choice set could potentially provide better coverage and capture the adaptive nature of route choice.
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| 39. |
- Ding-Mastera, Jing, et al.
(författare)
-
A latent-class adaptive routing choice model in stochastic time-dependent networks
- 2019
-
Ingår i: Transportation Research Part B. - : Elsevier. - 0191-2615 .- 1879-2367. ; 124, s. 1-17
-
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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| 40. |
- Do, Ron, et al.
(författare)
-
Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
-
Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 41. |
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| 42. |
- Du, QQ, et al.
(författare)
-
Generation of mega brown adipose tissue in adults by controlling brown adipocyte differentiation in vivo
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:40, s. e2203307119-
-
Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) is a highly specialized adipose tissue in its immobile location and size during the entire adulthood. In response to cold exposure and other β3-adrenoreceptor stimuli, BAT commits energy consumption by nonshivering thermogenesis (NST). However, the molecular machinery in controlling the BAT mass in adults is unknown. Here, we show our surprising findings that the BAT mass and functions can be manipulated in adult animals by controlling BAT adipocyte differentiation in vivo. Platelet-derived growth factor receptor α (PDGFα) expressed in BAT progenitor cells served a signaling function to avert adipose progenitor differentiation. Genetic and pharmacological loss-of-function of PDGFRα eliminated the differentiation barrier and permitted progenitor cell differentiation to mature and functional BAT adipocytes. Consequently, an enlarged BAT mass (megaBAT) was created by PDGFRα inhibition owing to increases of brown adipocyte numbers. Under cold exposure, a microRNA-485 (miR-485) was identified as a master suppressor of the PDGFRα signaling, and delivery of miR-485 also produced megaBAT in adult animals. Noticeably, megaBAT markedly improved global metabolism, insulin sensitivity, high-fat-diet (HFD)-induced obesity, and diabetes by enhancing NST. Together, our findings demonstrate that the adult BAT mass can be increased by blocking the previously unprecedented inhibitory signaling for BAT progenitor cell differentiation. Thus, blocking the PDGFRα for the generation of megaBAT provides an attractive strategy for treating obesity and type 2 diabetes mellitus (T2DM).
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| 43. |
- Feng, Chungang, et al.
(författare)
-
A cis-Regulatory Mutation of PDSS2 Causes Silky-Feather in Chickens
- 2014
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:8, s. e1004576-
-
Tidskriftsartikel (refereegranskat)abstract
- Silky-feather has been selected and fixed in some breeds due to its unique appearance. This phenotype is caused by a single recessive gene (hookless, h). Here we map the silky-feather locus to chromosome 3 by linkage analysis and subsequently fine-map it to an 18.9 kb interval using the identical by descent (IBD) method. Further analysis reveals that a C to G transversion located upstream of the prenyl (decaprenyl) diphosphate synthase, subunit 2 (PDSS2) gene is causing silky-feather. All silky-feather birds are homozygous for the G allele. The silky-feather mutation significantly decreases the expression of PDSS2 during feather development in vivo. Consistent with the regulatory effect, the C to G transversion is shown to remarkably reduce PDSS2 promoter activity in vitro. We report a new example of feather structure variation associated with a spontaneous mutation and provide new insight into the PDSS2 function.
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| 44. |
- Gao, Guangbin, et al.
(författare)
-
Understanding filamentous cyanobacteria and their adaptive niches in Lake Honghu, a shallow eutrophic lake
- 2025
-
Ingår i: Journal of Environmental Sciences (China). - 1001-0742. ; 152, s. 219-234
-
Tidskriftsartikel (refereegranskat)abstract
- Freshwater lakes globally are witnessing an escalation in the frequency and intensity of cyanobacterial harmful blooms. However, underlying factors influencing the succession or coexistence of cyanobacteria, especially filamentous ones, remain poorly understood. Lake Honghu, a Ramsar Wetland of International Importance with degrading aquatic ecological quality, served as a case study to elucidate the intricate relationship between environmental changes and cyanobacterial dynamics. Our analysis revealed a significant increase in the dominance of filamentous cyanobacteria, marked by high spatiotemporal variability in community structure. This dominance of filamentous diazotrophic cyanobacteria is attributed to a decrease in the ratio of dissolved inorganic nitrogen to total phosphorus and their capacity to utilize organic phosphorus in phosphorus-deficient conditions. Species-specific density variations were linked to diverse environmental factors, with total nitrogen or total phosphorus concentration remaining as a crucial factor influencing dominant cyanobacterial density fluctuations. The dominance of low-temperature-tolerant Aphanizomenon and Pseudanabaena was evident in spring and winter, whereas Dolichospermum and Cylindrospermopsis, which prefer higher temperatures, thrived in summer and autumn. Additionally, non-algal turbidity and heterogeneity can potentially alter the competitive outcome among filamentous cyanobacteria or foster coexistence under conditions of elevated temperatures and nutrient limitation. This study predicts that filamentous cyanobacteria may spread and persist in lakes spanning a wide trophic range. Current findings enhance our comprehension of the dynamic responses exhibited by filamentous bloom-forming cyanobacteria in the face of environmental changes within shallow eutrophic lakes and provide valuable insights for lake managers involved in the remediation of degraded shallow lakes.
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| 45. |
- Gao, Jiajia, et al.
(författare)
-
Light-induced electrolyte improvement in cobalt tris(bipyridine)-mediated dye-sensitized solar cells
- 2019
-
Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 7:33, s. 19495-19505
-
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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| 46. |
- Gao, Jie, et al.
(författare)
-
Phylogeography and introgression between Pinus kesiya and Pinus yunnanensis in Southeast Asia
- 2024
-
Ingår i: Journal of Systematics and Evolution. - : John Wiley & Sons. - 1674-4918 .- 1759-6831. ; 62:1, s. 120-134
-
Tidskriftsartikel (refereegranskat)abstract
- Southeast Asia (SEA) has seen strong climatic oscillations and fluctuations in sea levels during the Quaternary. The impact of past climate changes on the evolution and distribution of local flora in SEA is still poorly understood. Here we aim to infer how the Quaternary climate change affects the evolutionary process and range shifts in two pine species. We investigated the population genetic structure and diversity using cytoplasmic DNA markers, and performed ecological niche modeling to reconstruct the species past distribution and to project range shift under future climates. We found substantial gene flow across the continuous distribution of the subtropical Pinus yunnanensis. In contrast, the tropical Pinus kesiya showed a strong population structure in accordance with its disjunct distribution across montane islands in Indochina and the Philippines. A broad hybrid zone of the two species occurs in southern Yunnan. Asymmetric introgression from the two species was detected in this zone with dominant mitochondrial gene flow from P. yunnanensis and chloroplast gene flow from P. kesiya. The observed population structure suggests a typical postglaciation expansion in P. yunnanensis, and a glacial expansion and interglacial contraction in P. kesiya. Ecological niche modeling supports the inferred demographic history and predicts a decrease in range size for P. kesiya under future climates. Our results suggest that tropical pine species in SEA have undergone evolutionary trajectories different from high latitude species related to their Quaternary climate histories. We also illustrate the need for urgent conservation actions in this fragmented landscape.
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| 47. |
- Gao, Jing, et al.
(författare)
-
Solar Water Splitting with Perovskite/Silicon Tandem Cell and TiC-Supported Pt Nanocluster Electrocatalyst
- 2019
-
Ingår i: Joule. - : CELL PRESS. - 2542-4351. ; 3:12, s. 2930-2941
-
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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| 48. |
- 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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| 49. |
- Gao, Kai, et al.
(författare)
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Induction of Cytochrome P4501 Genes by Various Inducers in Rainbow Trout (Oncorhynchus mykiss)
- 2020
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Ingår i: Journal of Coastal Research. - : COASTAL EDUCATION & RESEARCH FOUNDATION. - 0749-0208 .- 1551-5036. ; 37:1, s. 143-148
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Tidskriftsartikel (refereegranskat)abstract
- Juvenile rainbow trout is widely found in various aquatic systems, such as freshwater, coastal, and marine habitats all over the world. Expression patterns of the cytochrome P4501 (CYP1) genes exposed to various stressors in such fish could be informative and useful in biomonitoring. In the present study, the induction of CYP1 in rainbow trout by indigo, humic acid (HA), and benzo(a)pyrene (BaP) was studied through a 12-hour exposure experiment by using rainbow trout as an experimental object. First, 7-ethoxyresorufin O-deethylase (EROD) activity and CYP1 expression levels in fish exposed to different concentrations of indigo were analyzed. The EROD activities in fish gills were greatly affected by the concentration of indigo (1, 18, 50, and 80 nM). The expression level of CYP1A1 and CYP1A3 in gills was higher compared with CYP1B1 and CYP1Cs. Second, the gill EROD activity and CYP1 mRNA expressions levels were compared when induced by indigo, HA, and BaP at the same concentration (1 nM). Results indicated that rainbow trout were sensitive to all three inducers. Among them, the HA affected CYP1A1 and CYP1A3 most obviously. CYP1A, as an important biomarker, was more sensitive than CYP1B and CYP1C to those inducers. The observed effects of the different CYP1 inducers could provide a useful tool for monitoring of AhR-active pollutants in the aquatic environment.
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| 50. |
- 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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