| 1. |
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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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| 11. |
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| 12. |
- Nie, Li Ying, et al.
(författare)
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High-Isolation Two-Port UWB Antenna Based on Shared Structure
- 2020
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Ingår i: IEEE Transactions on Antennas and Propagation. - 0018-926X. ; 68:12, s. 8186-8191
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Tidskriftsartikel (refereegranskat)abstract
- In this communication, a novel planar structure-shared diverse two-port ultrawideband (UWB) antenna with high isolation and common ground is proposed based on a new slot-loaded method. A tapered slot with an end-fire radiation pattern is etched in the top middle section of a coplanar waveguide (CPW)-fed printed monopole antenna to reduce its effects on the monopole mode. The two-port UWB antenna features diverse patterns which can fully cover the upper space. A nonuniformly symmetric-coupled coplanar waveguide (NSC-CPW) is introduced to enable the two sets of the feeding structures sharing a ground plane with minimum interaction. Due to the modal orthogonality, high isolation between the two ports is obtained without additional decoupling structures. The experimental results of the proposed multiple-input multiple-output (MIMO) antenna indicate that the isolation is higher than 31.4 dB and the diversity gain is approximately 10 dB within a wide frequency range from 2.98 to 10 GHz. Meanwhile, high realized peak gain (>2.5 dB) and good efficiency (>80%) are also obtained for both the ports.
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| 13. |
- Pettersson-Kymmer, Ulrika, et al.
(författare)
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HLA and KIR Associations of Cervical Neoplasia
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 218:12, s. 2006-2015
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognised by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.Methods: Here, we used HLA and KIR dosages imputed from SNP genotype data from 2,143 cervical neoplasia cases and 13,858 healthy controls of European decent.Results: Four novel HLA alleles were identified in association with cervical neoplasia: HLA-DRB3*9901 (OR=1.24, P=2.49×10-9), HLA-DRB5*0101 (OR=1.29, P=2.26×10-8), HLA-DRB5*9901 (OR=0.77, P=1.90×10-9) and HLA-DRB3*0301 (OR=0.63, P=4.06×10-5), due to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles. We also found homozygosity of HLA-C1 group alleles is a protective factor for HPV16-related cervical neoplasia (C1/C1, OR=0.79, P=0.005). This protective association was restricted to carriers of either KIR2DL2 (OR=0.67, P=0.00045) or KIR2DS2 (OR=0.69, P=0.0006).Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.
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| 14. |
- Sheng, Rongrong, et al.
(författare)
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Does hot weather affect work-related injury? A case-crossover study in Guangzhou, China
- 2018
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Ingår i: International Journal of Hygiene and Environmental Health. - : Elsevier BV. - 1438-4639. ; 221:3, s. 423-428
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite increasing concerns about the health effects of climate change, the extent to which workers are affected by hot weather is not well documented. This study aims to investigate the association between high temperatures and work-related injuries using data from a large subtropical city in China. Methods: We used workers’ compensation claims to identify work-related injuries in Guangzhou, China during 2011–2012. To feature the heat effect, the study period was restricted to the warm seasons in Guangzhou (1 May-31 October). We conducted a time-stratified case-crossover study to examine the association between ambient outdoor temperatures, including daily maximum and minimum temperatures, and cases of work-related injury. The relationships were assessed using conditional Poisson regression models. Results: Overall, a total of 5418 workers’ compensation claims were included over the study period. Both maximum and minimum temperatures were significantly associated with work-related injuries, but associations varied by subgroup. One °C increase in maximum temperature was associated with a 1.4% (RR = 1.014, 95%CIs 1.012–1.017) increase in daily injury claims. Significant associations were seen for male and middle-aged workers, workers in small and medium-sized enterprises, and those working in manufacturing sector. And 1 °C increase in minimum temperature was associated with 1.7% (RR = 1.017, 95%CIs 1.012–1.021) increase in daily injury claims. Significant associations were observed for female and middle-aged workers, workers in large-sized enterprises, and those working in transport and construction sectors. Conclusions: We found a higher risk of work-related injuries due to hot weather in Guangzhou, China. This study provides important epidemiological evidence for policy-makers and industry that may assist in the formulation of occupational safety and climate adaptation strategies.
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| 15. |
- Teng, Pengpeng, et al.
(författare)
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Degradation and self-repairing in perovskite light-emitting diodes
- 2021
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Ingår i: Matter. - : Elsevier. - 2590-2393 .- 2590-2385. ; 4:11, s. 3710-3724
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Tidskriftsartikel (refereegranskat)abstract
- One of the most critical challenges in perovskite light-emitting diodes (PeLEDs) lies in poor operational stability. Although field dependent ion migration is believed to play an important role in the operation of perovskite optoelectronic devices, a complete understanding of how it affects the stability of PeLEDs is still missing. Here, we report a unique self-repairing behavior that the electroluminescence of moderately degraded PeLEDs can almost completely restore to their initial performance after resting. We find that the accumulated halides within the hole transport layer undergo back diffusion toward the surface of the perovskite layer during resting, repairing the vacancies and thus resulting in electroluminescence recovery. These findings indicate that one of the dominant degradation pathways in PeLEDs is the generation of halide vacancies at perovskite/hole transport layer interface during operation. We thus further passivate this key interface, which results in a high external quantum efficiency of 22.8% and obviously improved operational stability.
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| 16. |
- Xiao, Wenming, et al.
(författare)
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Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1141-1150
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Tidskriftsartikel (refereegranskat)abstract
- Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing. Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
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| 17. |
- Xiong, Shaobing, et al.
(författare)
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Surface charge-transfer doping for highly efficient perovskite solar cells
- 2021
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Ingår i: Nano Energy. - : ELSEVIER. - 2211-2855 .- 2211-3282. ; 79
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Tidskriftsartikel (refereegranskat)abstract
- Nonradiative recombination losses are the predominant reason that limits the full thermodynamic potential of perovskite solar cells (PSCs), mainly originating from surface defects and interfacial energetics. However, their synergies between the two key factors are poorly understood. Herein, we systemically explore the energetic role of ionic liquid defect-passivator Tetrabutylammonium hexafluorophosphate (TBAPF(6)) on n-i-p planar PSCs. The perovskite film surface has been transformed from p-type to n-type after TBAPF(6) modification, evidenced by a shift of Fermi level closer to the conduction band. The n-type energetics result in a higher density of electron carrier and a smaller electron extraction barrier at perovskite/PCBM interface, promoting charge transport. It is also shown that the perovskite film can undergo a clear transformation from n-type to p-type character as increasing work function of substrates. Further studies clearly illustrate that TBAPF(6) not only reduces the surface defect-assisted recombination, but also restrains the interface carrier recombination. These combined effects lead to the effective suppression of nonradiative recombination, attributing to a significant improvement in the device power conversion efficiency.
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| 18. |
- Xu, Cang-Bao, et al.
(författare)
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Cigarette Smoke Extracts Promote Vascular Smooth Muscle Cell Proliferation and Enhances Contractile Responses in the Vasculature and Airway.
- 2010
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 107, s. 940-948
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Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoke exposure is a strong risk factor for cardiovascular and respiratory diseases. However, the knowledge about how cigarette smoke induces damage to vasculature and airway is limited. The present study was designed to examine the effects of cigarette smoke particles extracted by heptane (heptane-soluble smoke particles, HSP), by water (water-soluble smoke particles, WSP) and by DMSO (DMSO-soluble smoke particles, DSP), which represent lipophilic, hydrophilic and ambiphoteric constituents from the cigarette smoke, respectively. Human aortic smooth muscle cell (HASMC) proliferation was assessed in cell culture. Rat resistance artery and airway contractile responses to serotonin, U46619, phenylephrine, noradrenaline, acetylcholine, des-Arg(9)-bradykinin, bradykinin, sarafotoxin 6c and endothelin-1 were monitored by a sensitive myograph system. Immunocytochemistry and cell-based phosphoELISA assay were used to demonstrate activation of extracellular signal-regulated kinases 1/2 (ERK1/2). For the first time, our results demonstrate that although all the three extracts promote HASMC proliferation, the HSP and DSP effects occur earlier. HSP and DSP, but not WSP, increase the contractile responses to sarafotoxin 6c, U46619 or bradykinin in rat mesenteric artery and/or in bronchi. ERK1/2 is activated by HSP and DSP in HASMCs and inhibition of ERK1/2 abrogated the smoke extracts-induced HASMC proliferation, while blockage of nicotinic receptors had no effects, suggesting that the toxic effects of the smoke extracts occur via activation of intracellular ERK1/2 signalling, but not nicotinic receptors.
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| 19. |
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| 20. |
- Zhang, Wei, et al.
(författare)
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Activation of nuclear factor-kappa B pathway is responsible for tumor necrosis factor-a-induced up-regulation of endothelin B2 receptor expression in vascular smooth muscle cells in vitro
- 2012
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Ingår i: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 209:2, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- The endothelin B2 (ETB2) receptors are induced in vascular smooth muscle cells (VSMCs) in cardiovascular diseases. We tested if in vitro short-term exposure to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) could up-regulate ETB2 receptors in rat mesenteric arteries, and if this effect is through activation of intracellular nuclear factor-kappa B (NF-kappa B) pathway. The mesenteric arteries were dissected from male Sprague-Dawley rats and the endothelium was removed. The arteries were co-incubated with TNF-alpha in serum-free Dulbecco's modified Eagle's medium. Real-time reverse transcription-PCR, Western blot and immunohistochemical staining were employed to assess the mRNA/protein expression of ETB2 receptors and activation of NF-kappa B pathway. The results showed that, during organ culture. TNF-alpha concentration-dependently enhanced ET52 receptors expression at both mRNA and protein levels, paralleled with activation of NF-kappa B pathway in VSMC. The up-regulated ETB2 receptor expression and NF-kappa B activation could be effectively suppressed by general transcriptional inhibitor actinomycin D, or either of the selective I kappa B kinase inhibitors wedelolactone and IMD-0354. Conclusively, the activation of intracellular NF-kappa B pathway is responsible for the up-regulation of ETB2 receptors induced by short-term exposure to TNF-alpha. This could partly explain the toxic effects of TNF-alpha on VSMCs that account for cardiovascular diseases. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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