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| 2. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 3. |
- Bao, Chunxiong, et al.
(författare)
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Bidirectional optical signal transmission between two identical devices using perovskite diodes
- 2020
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Ingår i: NATURE ELECTRONICS. - : NATURE PUBLISHING GROUP. - 2520-1131. ; 3:3, s. 156-164
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Tidskriftsartikel (refereegranskat)abstract
- A solution-processed perovskite diode that functions as both optical transmitter and receiver can be used to build a monolithic pulse sensor and a bidirectional optical communication system. The integration of optical signal generation and reception into one device-thus allowing a bidirectional optical signal transmission between two identical devices-is of value in the development of miniaturized and integrated optoelectronic devices. However, conventional solution-processable semiconductors have intrinsic material and design limitations that prevent them from being used to create such devices with a high performance. Here we report an efficient solution-processed perovskite diode that is capable of working in both emission and detection modes. The device can be switched between modes by changing the bias direction, and it exhibits light emission with an external quantum efficiency of over 21% and a light detection limit on a subpicowatt scale. The operation speed for both functions can reach tens of megahertz. Benefiting from the small Stokes shift of perovskites, our diodes exhibit a high specific detectivity (more than 2 x 10(12) Jones) at its peak emission (~804 nm), which allows an optical signal exchange between two identical diodes. To illustrate the potential of the dual-functional diode, we show that it can be used to create a monolithic pulse sensor and a bidirectional optical communication system.
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| 4. |
- Bao, Ying, et al.
(författare)
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Folate Intake and Risk of Pancreatic Cancer : Pooled Analysis of Prospective Cohort Studies
- 2011
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Ingår i: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 103:24, s. 1840-1850
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Forskningsöversikt (refereegranskat)abstract
- Background Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. Methods We analyzed primary data from 14 prospective cohort studies that included 319 716 men and 542 948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. Results During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P-trend = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P-trend = .90). No between-study heterogeneity was observed (for dietary folate, P-heterogeneity = .15; for total folate, P-heterogeneity = .22). Conclusion Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.
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| 5. |
- Fang, Li Tai, et al.
(författare)
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Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1151-1160
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking 'tumor-only' or 'matched tumor-normal' analyses. The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
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| 6. |
- Lei, Ying, et al.
(författare)
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Enhanced airway smooth muscle cell thromboxane receptor signaling via activation of JNK MAPK and extracellular calcium influx.
- 2011
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 650:2-3, s. 629-638
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Tidskriftsartikel (refereegranskat)abstract
- Thromboxane is a key inflammatory mediator and potent airway constrictor. It acts on thromboxane A(2) (TP) receptors and contributes to airway inflammation and airway hyperresponsiveness that is the characteristic feature of asthma. The present study was designed to study TP receptor signaling in airway smooth muscle cells by using an organ culture model and a set of selective pharmacological inhibitors for mitogen-activated protein kinase (MAPK) and calcium signal pathways. Western-blot, immunohistochemistry, myograph and a selective TP receptor agonist U46619 were used for examining TP receptor signal proteins and function. Organ culture of rat bronchial segments for up to 48h induces a time-dependently increased airway contractile response to U46619. This indicates that organ culture increases TP receptor signaling in the airway smooth muscle cells. The enhanced bronchial contraction was attenuated by the inhibition of c-Jun N-terminal kinase (JNK) MAPK activity, chelation of extracellular calcium and calcium channel blocker nifedipine, suggesting that JNK MAPK activity and elevated intracellular calcium level are required for the TP receptor signaling. In conclusion, airway smooth muscle cell TP receptor signaling occurs via JNK MAPK activity and the elevation of extracellular calcium influx, which may provide knowledge for understanding the signaling pathway responsible for the modulation of TP receptor mediated airway hyperresponsiveness to thromboxane.
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| 7. |
- Lei, Ying, et al.
(författare)
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The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice
- 2008
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sidestream smoke is closely associated with airway inflammation and hyperreactivity. The present study was designed to investigate if the Raf-1 inhibitor GW5074 and the anti-inflammatory drug dexamethasone suppress airway hyperreactivity in a mouse model of sidestream smoke exposure. Methods: Mice were repeatedly exposed to smoke from four cigarettes each day for four weeks. After the first week of the smoke exposure, the mice received either dexamethasone intraperitoneally every other day or GW5074 intraperitoneally every day for three weeks. The tone of the tracheal ring segments was recorded with a myograph system and concentration-response curves were obtained by cumulative administration of agonists. Histopathology was examined by light microscopy. Results: Four weeks of exposure to cigarette smoke significantly increased the mouse airway contractile response to carbachol, endothelin-1 and potassium. Intraperitoneal administration of GW5074 or dexamethasone significantly suppressed the enhanced airway contractile responses, while airway epithelium-dependent relaxation was not affected. In addition, the smoke-induced infiltration of inflammatory cells and mucous gland hypertrophy were attenuated by the administration of GW5074 or dexamethasone. Conclusion: Sidestream smoke induces airway contractile hyperresponsiveness. Inhibition of Raf-1 activity and airway inflammation suppresses smoking-associated airway hyperresponsiveness.
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| 8. |
- Lei, Ying, et al.
(författare)
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Up-regulation of bradykinin receptors in rat bronchia via IkappaB kinase-mediated inflammatory signaling pathway.
- 2010
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 634:1-3, s. 149-161
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Tidskriftsartikel (refereegranskat)abstract
- IkappaB kinase (IKK)-mediated intracellular signaling mechanisms may be involved in airway hyperresponsiveness through up-regulation of bradykinin receptors. This study was designed to examine if organ culture of rat bronchial segments induces airway hyperresponsiveness to bradykinin and if inhibition of IKK can abrogate the airway hyperresponsiveness to bradykinin via suppressing the expression of bradykinin B(1) and B(2) receptors. Rat bronchi were isolated and cut into ring segments. The segments were then organ cultured in the presence or absence of IKK inhibitors, BMS-345541 or TPCA-1. des-Arg(9)-bradykinin (B(1) receptor agonist) - and bradykinin (B(2) receptor agonist) - induced contractions of the segments were monitored by a sensitive organ bath system. The expression of bradykinin B(1) and B(2) receptors, inflammatory mediators and phosphorylated IKK were studied by a real-time PCR and/or by immunohistochemistry using confocal microscopy. Organ culture of the bronchial segments induced a time-dependent up-regulation of bradykinin B(1) and B(2) receptors. The IKK inhibitors abolished the organ culture-induced up-regulation of bradykinin B(1) and B(2) receptor-mediated contractions in a concentration-dependent manner. This was paralleled with inhibition of IKK activity (phosphorylation), reduced mRNA and protein expressions of bradykinin B(1) and B(2) receptors and decreased mRNA expression of inflammatory mediators (interleukin-6, inducible nitric oxide synthase, cyclooxygenase 2 and matrix metalloproteinase 9). Our results show that organ culture induces IKK-mediated inflammatory changes in airways which subsequently results in airway hyperresponsiveness to bradykinin via the up-regulated bradykinin receptors. Thus, IKK inhibition might be a promising approach for treatment of airway inflammation and airway hyperresponsiveness that are often seen in asthmatic patients.
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| 9. |
- Li, Guoshuai, et al.
(författare)
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Site selection of desert solar farms based on heterogeneous sand flux
- 2024
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Ingår i: npj Climate and Atmospheric Science. - 2397-3722. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Site selection for building solar farms in deserts is crucial and must consider the dune threats associated with sand flux, such as sand burial and dust contamination. Understanding changes in sand flux can optimize the site selection of desert solar farms. Here we use the ERA5-Land hourly wind data with 0.1° × 0.1° resolution to calculate the yearly sand flux from 1950 to 2022. The mean of sand flux is used to score the suitability of global deserts for building solar farms. We find that the majority of global deserts have low flux potential (≤ 40 m3 m-1 y-1) and resultant flux potential (≤ 2.0 m3 m-1 y-1) for the period 1950–2022. The scoring result demonstrates that global deserts have obvious patchy distribution of site suitability for building solar farms. Our study contributes to optimizing the site selection of desert solar farms, which aligns with the United Nations sustainability development goals for achieving affordable and clean energy target by 2030.
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| 10. |
- Liu, Min, et al.
(författare)
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Density Functional Theory Study of Influence of Oxide Thickness and Surface Alloying on Cl Migration within alpha-Al2O3
- 2021
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 168:8
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Tidskriftsartikel (refereegranskat)abstract
- Insertion and migration of chlorine atoms (Cl) in alpha-Al2O3 were studied by density functional theory calculations focusing on the influence of oxide thickness and doping by Mg, Cu and Si. Work function, electronic band gap, and insertion energy were calculated to explore thermodynamics of Cl migration. Partial density of state (PDOS) calculations revealed the role of dopants in the electronic character of metal-O and Al-Cl bonds. Work function data showed the effect of Cl insertion into the oxide film on the corrosion resistance. Cl can locate at an O vacancy (V-O) with a large exothermic insertion energy, independent of oxide thickness, but can only locate at superficial Al vacancy (V-Al) exothermically. The energy barrier for Cl migration via neighboring V-O increases with oxide thickness, and is 2 similar to 2.5 eV for thicker oxides. Cl insertion causes a work function reduction exceeding 2 eV, implying a decreased corrosion resistance. The inhibition of Cl migration by Si-doping can be explained by a more intense hybridization peak of Si-O over Al-O in the PDOS profile, while the reduction of energy barrier by Mg-/Cu-doping probably is due to the deviation of metal-s state from the Fermi energy, thus facilitating Cl movement within the oxide.
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