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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- Wheeler, Eleanor, et al.
(författare)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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- Chen, Huang, et al.
(författare)
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A portable micro glucose sensor based on copper-based nanocomposite structure
- 2019
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Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1369-9261 .- 1144-0546. ; 43:20, s. 7806-7813
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Tidskriftsartikel (refereegranskat)abstract
- Precisely detecting the concentration of glucose in the human body is an attractive way to prevent or treat diabetes. Portable glucose sensors with non-enzymatic catalytic materials have received great attention in recent years. Herein, a facile strategy for fabricating a high-performance electrochemical sensor is proposed. A non-enzymatic three-electrode integrated glucose sensor device based on CuO nano-coral arrays/nanoporous Cu (NCA/NPC) is designed and fabricated. The portable NCA/NPC glucose sensor device exhibits high catalytic activity for glucose. The great performance of the NCA/NPC glucose sensor device derives from the excellent conductivity of the NPC substrate and the high electrocatalytic activity of CuO nano-coral arrays. This device exhibits a high sensitivity of 1621 μA mM -1 cm -2 in the linear range of 0.0005-5.0 mM, low detection limit of 200 nM (S/N = 3), fast response time of 3 s, good anti-interference performance, excellent repeatability and considerable stability for glucose detection. This work will certainly provide an efficient structure and proper catalytic material choices for future non-enzymatic glucose sensors.
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| 6. |
- Dong, Y. B., et al.
(författare)
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Transfer-free, lithography-free, and micrometer-precision patterning of CVD graphene on SiO 2 toward all-carbon electronics
- 2018
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Ingår i: APL Materials. - : AIP Publishing. - 2166-532X. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- A method of producing large area continuous graphene directly on SiO 2 by chemical vapor deposition is systematically developed. Cu thin film catalysts are sputtered onto the SiO 2 and pre-patterned. During graphene deposition, high temperature induces evaporation and balling of the Cu, and the graphene "lands onto" SiO 2 . Due to the high heating and growth rate, continuous graphene is largely completed before the Cu evaporation and balling. 60 nm is identified as the optimal thickness of the Cu for a successful graphene growth and μm-large feature size in the graphene. An all-carbon device is demonstrated based on this technique.
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| 7. |
- Dong, Yibo, et al.
(författare)
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Transfer-free, lithography-free and fast growth of patterned CVD graphene directly on insulators by using sacrificial metal catalyst
- 2018
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Ingår i: Nanotechnology. - : IOP Publishing. - 1361-6528 .- 0957-4484. ; 29:36
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Tidskriftsartikel (refereegranskat)abstract
- Chemical vapor deposited graphene suffers from two problems: transfer from metal catalysts to insulators, and photoresist induced degradation during patterning. Both result in macroscopic and microscopic damages such as holes, tears, doping, and contamination, translated into property and yield dropping. We attempt to solve the problems simultaneously. A nickel thin film is evaporated on SiO2 as a sacrificial catalyst, on which surface graphene is grown. A polymer (PMMA) support is spin-coated on the graphene. During the Ni wet etching process, the etchant can permeate the polymer, making the etching efficient. The PMMA/graphene layer is fixed on the substrate by controlling the surface morphology of Ni film during the graphene growth. After etching, the graphene naturally adheres to the insulating substrate. By using this method, transfer-free, lithography-free and fast growth of graphene realized. The whole experiment has good repeatability and controllability. Compared with graphene transfer between substrates, here, no mechanical manipulation is required, leading to minimal damage. Due to the presence of Ni, the graphene quality is intrinsically better than catalyst-free growth. The Ni thickness and growth temperature are controlled to limit the number of layers of graphene. The technology can be extended to grow other two-dimensional materials with other catalysts.
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| 8. |
- Fan, Chuan Gang, et al.
(författare)
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Experimental study of sidewall effect on flame characteristics of heptane pool fires with different aspect ratios and orientations in a channel
- 2017
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Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489 .- 1873-2704. ; 36:2, s. 3121-3129
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Tidskriftsartikel (refereegranskat)abstract
- A series of small scale tests was conducted to investigate the influence of sidewall on flame characteristics of heptane pool fires in a channel, considering pool shape (aspect ratio: 1, 2, 4 and 8) and pool orientation relative to sidewall. Distance between fire and sidewall was changed systematically. Both transverse flame development (along the direction of channel width) and longitudinal flame development (along the direction of channel length) were recorded by digital video. Results show that for a fixed fire location, the heat release rate increases with the increasing pool aspect ratio (namely a larger pool perimeter), which indicates more air entrainment and more intense combustion. In wall fire cases, when the long pool rim is perpendicular with channel sidewall, the flame can obtain more air entrainment with a weaker boundary restriction from the sidewall, compared to the case with the long pool rim being parallel with sidewall. Comparison of some previously established correlations based on various experimental conditions with our test results is made. Due to the fact without considering sidewall effect and fuel shape on the air entrainment of fire plume, the classic correlations need to be further improved. Therefore, an integral flame length model considering both sidewall effect and fuel shape is developed, which correlates well with all the data from cases with various pool positions, orientations and aspect ratios. © 2016 The Combustion Institute. Published by Elsevier Inc.
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| 9. |
- Ji, Jie, et al.
(författare)
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Experimental study of non-monotonous sidewall effect on flame characteristics and burning rate of n-heptane pool fires
- 2015
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361 .- 1873-7153. ; 145, s. 228-233
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Tidskriftsartikel (refereegranskat)abstract
- To study the influence of sidewall effect on flame characteristics and burning rate, a series of experiments with heptane pools was conducted. The results showed that as the fires were placed close to the sidewall, the flames inclined to the sidewall due to the restriction on air entrainment, and the burning rate increased on the whole, which could be mainly due to the enhanced radiation from the heated sidewall and ceiling flame. However, regardless of fuel pool shape, the burning rate obtained the peak value when the fire was near the sidewall, rather than attached to the sidewall, resulting from less flame radiation from the vertical flame part to the fuel in the latter case. The ratio of longitudinal ceiling flame length to transverse length tended to decrease with the fire moving close to the sidewall. For cases with the largest length and wall fires, the ratio was nearly 0.5, which could be explained according to the theory of mirror effect. Also, due to the non-monotonous sidewall effect, a higher burning rate did not necessarily lead to a larger ceiling flame length.
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| 10. |
- Kuo, Chih-Hsi S., et al.
(författare)
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Contribution of airway eosinophils in airway wall remodeling in asthma : Role of MMP-10 and MET
- 2019
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 74:6, s. 1102-1112
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Tidskriftsartikel (refereegranskat)abstract
- Background Eosinophils play an important role in the pathophysiology of asthma being implicated in airway epithelial damage and airway wall remodeling. We determined the genes associated with airway remodeling and eosinophilic inflammation in patients with asthma. Methods We analyzed the transcriptomic data from bronchial biopsies of 81 patients with moderate-to-severe asthma of the U-BIOPRED cohort. Expression profiling was performed using Affymetrix arrays on total RNA. Transcription binding site analysis used the PRIMA algorithm. Localization of proteins was by immunohistochemistry. Results Using stringent false discovery rate analysis, MMP-10 and MET were significantly overexpressed in biopsies with high mucosal eosinophils (HE) compared to low mucosal eosinophil (LE) numbers. Immunohistochemical analysis confirmed increased expression of MMP-10 and MET in bronchial epithelial cells and in subepithelial inflammatory and resident cells in asthmatic biopsies. Using less-stringent conditions (raw P-value < 0.05, log2 fold change > 0.5), we defined a 73-gene set characteristic of the HE compared to the LE group. Thirty-three of 73 genes drove the pathway annotation that included extracellular matrix (ECM) organization, mast cell activation, CC-chemokine receptor binding, circulating immunoglobulin complex, serine protease inhibitors, and microtubule bundle formation pathways. Genes including MET and MMP10 involved in ECM organization correlated positively with submucosal thickness. Transcription factor binding site analysis identified two transcription factors, ETS-1 and SOX family proteins, that showed positive correlation with MMP10 and MET expression. Conclusion Pathways of airway remodeling and cellular inflammation are associated with submucosal eosinophilia. MET and MMP-10 likely play an important role in these processes.
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