| 1. |
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- 2019
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Journal article (peer-reviewed)
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| 2. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Takeuchi, Fumihiko, et al.
(author)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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| 4. |
- Weinstein, John N., et al.
(author)
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The cancer genome atlas pan-cancer analysis project
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 5. |
- Demerath, Ellen W., et al.
(author)
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Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci
- 2015
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:15, s. 4464-4479
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Journal article (peer-reviewed)abstract
- Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed-effects regression models were used to test the association of methylation beta value with concurrent body mass index (BMI) and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole-blood DNA from 2377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the Genetics of Lipid Lowering Drugs and Diet Network Study was followed by testing using adipose tissue DNA from 648 women in the Multiple Tissue Human Expression Resource cohort. Seventy-six BMI-related probes, 164 WC-related probes and 8 BMI change-related probes passed the threshold for significance in ARIC (P < 1 x 10(-7); Bonferroni), including probes in the recently reported HIF3A, CPT1A and ABCG1 regions. Replication using blood DNA was achieved for 37 BMI probes and 1 additional WC probe. Sixteen of these also replicated in adipose tissue, including 15 novel methylation findings near genes involved in lipid metabolism, immune response/cytokine signaling and other diverse pathways, including LGALS3BP, KDM2B, PBX1 and BBS2, among others. Adiposity traits are associated with DNA methylation at numerous CpG sites that replicate across studies despite variation in tissue type, ethnicity and analytic approaches.
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| 6. |
- Shrine, Nick, et al.
(author)
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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
- 2019
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
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Journal article (peer-reviewed)abstract
- Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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| 7. |
- Watts, Anna L., et al.
(author)
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Dense matter with eXTP
- 2019
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In: Science China Physics, Mechanics & Astronomy. - : Science Press. - 1674-7348 .- 1869-1927. ; 62:2
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Research review (peer-reviewed)abstract
- In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Sciences, the eXTP mission is expected to be launched in the mid 2020s.
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| 8. |
- Zhang, Kaicheng, et al.
(author)
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SN 2014J in M82 : new insights on the spectral diversity of Type Ia supernovae
- 2018
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 481:1, s. 878-893
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Journal article (peer-reviewed)abstract
- We present extensive spectroscopic observations for one of the closest Type Ia supernovae (SNe Ia), SN 2014J discovered in M82, ranging from 10.4 d before to 473.2 d after B-band maximum light. The diffuse interstellar band features detected in a high-resolution spectrum allow an estimate of line-of-sight extinction as A(v) similar to 1.9 +/- 0.6 mag. Spectroscopically, SN 2014J can be put into the high-velocity (HV) subgroup in Wang's classification with a velocity of Si II lambda 6355 at maximum light of upsilon(0) = 1.22 +/- 0.01 x 10(4) km s(-1) but has a low velocity gradient (LVG, following Benetti's classification) of (v) over bar = 41 +/- 2 km s(-1) d(-1), which is inconsistent with the trend that HV SNe Ia generally have larger velocity gradients. We find that the HV SNe Ia with LVGs tend to have relatively stronger Si III (at similar to 4400 angstrom) absorptions in early spectra, larger ratios of S II lambda 5468 to S II lambda 5640, and weaker Si II 5972 absorptions compared to their counterparts with similar velocities but high velocity gradients. This shows that the HV+ LVG subgroup of SNe Ia may have intrinsically higher photospheric temperature, which indicates that their progenitors may experience more complete burning in the explosions relative to the typical HV SNe Ia.
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| 9. |
- Arcavi, Iair, et al.
(author)
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Energetic eruptions leading to a peculiar hydrogen-rich explosion of a massive star
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7679, s. 210-213
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Journal article (peer-reviewed)abstract
- Every supernova so far observed has been considered to be the terminal explosion of a star. Moreover, all supernovae with absorption lines in their spectra show those lines decreasing in velocity over time, as the ejecta expand and thin, revealing slower-moving material that was previously hidden. In addition, every supernova that exhibits the absorption lines of hydrogen has one main light-curve peak, or a plateau in luminosity, lasting approximately 100 days before declining(1). Here we report observations of iPTF14hls, an event that has spectra identical to a hydrogen-rich core-collapse supernova, but characteristics that differ extensively from those of known supernovae. The light curve has at least five peaks and remains bright for more than 600 days; the absorption lines show little to no decrease in velocity; and the radius of the line-forming region is more than an order of magnitude bigger than the radius of the photosphere derived from the continuum emission. These characteristics are consistent with a shell of several tens of solar masses ejected by the progenitor star at supernova-level energies a few hundred days before a terminal explosion. Another possible eruption was recorded at the same position in 1954. Multiple energetic pre-supernova eruptions are expected to occur in stars of 95 to 130 solar masses, which experience the pulsational pair instability(2-5). That model, however, does not account for the continued presence of hydrogen, or the energetics observed here. Another mechanism for the violent ejection of mass in massive stars may be required.
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| 10. |
- Li, Danqin, et al.
(author)
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n-Doping of photoactive layer in binary organic solar cells realizes over 18.3% efficiency
- 2022
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In: Nano Energy. - : ELSEVIER. - 2211-2855 .- 2211-3282. ; 96
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Journal article (peer-reviewed)abstract
- Electronic doping of conjugated semiconductor plays a critical role in the fabrication of high efficiency organic optoelectronic devices. Here, we report an organic solar cell (OSC) by doping n-type DMBI-BDZC into one host binary bulk heterojunction (BHJ) photoactive layer comprised of a polymer donor PM6 and a nonfullerene acceptor Y6. The resulting champion device yields a significantly improved power conversion efficiency from 17.17% to 18.33% with an impressive fill factor of 80.20%. It is found that the electrically doped photoactive layer exhibits enhanced and balanced charge carrier mobilities, more effective exciton dissociation, longer carrier lifetime, and suppressed charge recombination with smaller energy loss. The dopant molecule DMBIBDZC also act as a surface morphology modifier of the photoactive layer with enhanced charge transport. This work demonstrates that manipulation of charge transport via adding a low concentration dopant into photoactive layer is a promising approach for further improvement of BHJ OSC performance.
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| 11. |
- Merino, Jordi, et al.
(author)
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Polygenic scores, diet quality, and type 2 diabetes risk : An observational study among 35,759 adults from 3 US cohorts
- 2022
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 19:4
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Journal article (peer-reviewed)abstract
- Background Bothgenetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. Methods and findings We analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. WAU ith: Pleas over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. Conclusions These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk.
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| 12. |
- Qi, Qibin, et al.
(author)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Journal article (peer-reviewed)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 13. |
- Schunkert, Heribert, et al.
(author)
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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
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Journal article (peer-reviewed)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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| 14. |
- Tong, Yang, et al.
(author)
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Progress of the key materials for organic solar cells
- 2020
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In: Science in China Series B. - Beijing, China : SCIENCE PRESS. - 1674-7291 .- 1869-1870. ; 63:6, s. 758-765
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Research review (peer-reviewed)abstract
- Organic solar cells have attracted academic and industrial interests due to the advantages like lightweight, flexibility and roll-to-roll fabrication. Nowadays, 18% power conversion efficiency has been achieved in the state-of-the-art organic solar cells. The recent rapid progress in organic solar cells relies on the continuously emerging new materials and device fabrication technologies, and the deep understanding on film morphology, molecular packing and device physics. Donor and acceptor materials are the key materials for organic solar cells since they determine the device performance. The past 25 years have witnessed an odyssey in developing high-performance donors and acceptors. In this review, we focus on those star materials and milestone work, and introduce the molecular structure evolution of key materials. These key materials include homopolymer donors, D-A copolymer donors, A-D-A small molecular donors, fullerene acceptors and nonfullerene acceptors. At last, we outlook the challenges and very important directions in key materials development.
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| 15. |
- Zhao, Yaofeng, et al.
(author)
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Ornithorhynchus anatinus (Platypus) Links the Evolution of Immunoglobulin Genes in Eutherian Mammals and Nonmammalian Tetrapods
- 2009
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 183:5, s. 3285-3293
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Journal article (peer-reviewed)abstract
- The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an mu-delta-o-gamma 2-gamma 1-alpha 1-epsilon-alpha 2 order, spanning a total of similar to 200 kb DNA, encoding six distinct isotypes. The o (o for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to nu (epsilon) and gamma, and thus appears to be a structural intermediate between these two genes. The platypus delta gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammallian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.
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| 16. |
- Andrews, Jennifer E., et al.
(author)
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SN 2017gmr : An Energetic Type II-P Supernova with Asymmetries
- 2019
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 885:1
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Journal article (peer-reviewed)abstract
- We present high-cadence UV, optical, and near-infrared data on the luminous Type II-P supernova SN;2017gmr from hours after discovery through the first 180 days. SN;2017gmr does not show signs of narrow, high-ionization emission lines in the early optical spectra, yet the optical light-curve evolution suggests that an extra energy source from circumstellar medium (CSM) interaction must be present for at least 2 days after explosion. Modeling of the early light curve indicates a ?500 R progenitor radius, consistent with a rather compact red supergiant, and late-time luminosities indicate that up to 0.130;;0.026 M of Ni-56 are present, if the light curve is solely powered by radioactive decay, although the Ni-56 mass may be lower if CSM interaction contributes to the post-plateau luminosity. Prominent multipeaked emission lines of H? and [O i] emerge after day 154, as a result of either an asymmetric explosion or asymmetries in the CSM. The lack of narrow lines within the first 2 days of explosion in the likely presence of CSM interaction may be an example of close, dense, asymmetric CSM that is quickly enveloped by the spherical supernova ejecta.
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| 17. |
- Assimes, Themistocles L., et al.
(author)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Journal article (peer-reviewed)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 18. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 19. |
- Cai, Liming, et al.
(author)
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Optimal control of a malaria model with asymptomatic class and superinfection
- 2017
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In: Mathematical Biosciences. - : Elsevier BV. - 0025-5564 .- 1879-3134. ; 288, s. 94-108
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Journal article (peer-reviewed)abstract
- In this paper, we introduce a malaria model with an asymptomatic class in human population and exposed classes in both human and vector populations. The model assumes that asymptomatic individuals can get re-infected and move to the symptomatic class. In the case of an incomplete treatment, symptomatic individuals move to the asymptomatic class. If successfully treated, the symptomatic individuals recover and move to the susceptible class. The basic reproduction number, R0,R0, is computed using the next generation approach. The system has a disease-free equilibrium (DFE) which is locally asymptomatically stable when R0<1,R0<1, and may have up to four endemic equilibria. The model exhibits backward bifurcation generated by two mechanisms; standard incidence and superinfection. If the model does not allow for superinfection or deaths due to the disease, then DFE is globally stable which suggests that backward bifurcation is no longer possible. Simulations suggest that total prevalence of malaria is the highest if all individuals show symptoms upon infection, but then undergoes an incomplete treatment and the lowest when all the individuals first move to the symptomatic class then treated successfully. Total prevalence is average if more individuals upon infection move to the asymptomatic class. We study optimal control strategies applied to bed-net use and treatment as main tools for reducing the total number of symptomatic and asymptomatic individuals. Simulations suggest that the optimal control strategies are very dynamic. Although they always lead to decrease in the symptomatic infectious individuals, they may lead to increase in the number of asymptomatic infectious individuals. This last scenario occurs if a large portion of newly infected individuals move to the symptomatic class but many of them do not complete treatment or if they all complete treatment but the superinfection rate of asymptomatic individuals is average.
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| 20. |
- Du, Kun, et al.
(author)
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Effects of the layout of film holes near the vane leading edge on the endwall cooling and phantom cooling of the vane suction side surface
- 2017
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In: Numerical Heat Transfer; Part A: Applications. - : Informa UK Limited. - 1040-7782 .- 1521-0634. ; 71:9, s. 910-927
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Journal article (peer-reviewed)abstract
- In the current research, effects of the layout of film holes near the first-stage vane leading edge on the endwall cooling and phantom cooling of the vane suction side surface were numerically studied. The computational results indicate that the case with a positive film-hole angle achieves a higher cooling effectiveness level on the endwall and vane suction side surface compared to the case with a corresponding negative film-hole angle. Furthermore, the location of the film hole has a significant influence on the cooling performance of the endwall and vane suction side surface. In addition, the case with a smaller distance from film holes to the vane stagnation also attains a slightly higher cooling effectiveness (phantom cooling effectiveness) on the vane suction side surface.
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| 21. |
- Du, Kun, et al.
(author)
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Effects of the mainstream turbulence intensity and slot injection angle on the endwall cooling and phantom cooling of the vane suction side surface
- 2017
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In: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310. ; 112, s. 427-440
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Journal article (peer-reviewed)abstract
- In order to obtain better performance, gas turbines always operate with high inlet temperature. This contributes to a high level of thermal load on the first stage vane endwall. To ensure safe operation of a gas turbine within a proper temperature range, the cooling performance of the vane endwall must be further investigated. In the present study, effects of the mainstream turbulence and upstream coolant flow direction on the endwall cooling and vane suction side surface phantom cooling were numerically investigated. Three-dimensional (3D) Reynolds-averaged Navier–Stokes (RANS) equations combined with shear stress transport (SST) k-ω turbulence model were solved to conduct the numerical simulations on basis of the validated turbulence model. The calculated results indicate that both the adiabatic cooling effectiveness on the endwall and the phantom cooling effectiveness on the vane suction side surface are significantly influenced by slot injection angle. For α=-30°, the coolant injection is driven towards the vane suction side, which contributes to the lowest adiabatic cooling effectiveness level on the pressure side endwall and the highest phantom cooling effectiveness level on the vane suction side surface. With the increase of the slot injection angle, the adiabatic cooling effectiveness level on the pressure side endwall is enhanced significantly. In contrast, the phantom cooling (when the vane suction side is cooled by coolant originating from the endwall) of the vane suction side surface is reduced significantly. This is because a large slot injection angle leads to a large coolant momentum towards the pressure side. Moreover, the case with a smaller slot injection angle obtains a slightly higher area-averaged adiabatic cooling effectiveness level around the leading edge due to a relatively larger portion of coolant being confined near the leading edge. In addition, the inlet turbulence intensity has a small impact on the overall endwall cooling and the phantom cooling of the vane suction side surface compared to the slot injection angle.
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| 22. |
- Freitag, Daniel F., et al.
(author)
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Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
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In: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
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Journal article (peer-reviewed)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
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| 23. |
- Gaulton, Kyle J, et al.
(author)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Journal article (peer-reviewed)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 24. |
- Geng, Xiumei, et al.
(author)
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Bioinspired Ultrastable Lignin Cathode via Graphene Reconfiguration for Energy Storage
- 2017
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In: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 5:4, s. 3553-3561
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Journal article (peer-reviewed)abstract
- Lignin extracted from trees is one of the most abundant biopolymers on Earth. Quinone, a sub-structure in lignin, can be used for energy storage via reversible redox reactions through absorbing and releasing electrons and protons. However, these efforts have encountered hindrances, such as short life cycle, low cycling efficiency, and a high self-discharge rate. All of these issues are related to electrode dissolution by electrolyte solvents and the insulating nature of lignin. Addressing these critical challenges, for the first time we use a reconfigurable and hierarchical graphene cage to capture the lignin by mimicking the prey-trapping of venus flytraps. The reconfigurable graphene confines the lignin within the electrode to prevent its dissolution, while acting as a three-dimensional current collector to provide efficient electron transport pathways during the electrochemical reactions. This bioinspired design enables the best cycling performance of lignin reported so far at 88% capacitance retention for 15000 cycles and 211 F g-1 capacitance at a current density of 1.0 A g-1. This study demonstrates a feasible and effective strategy for solving the long-term cycling difficulties of lignin-based electrochemically active species, and makes it possible to utilize lignin as an efficient, cheap, and renewable energy storage material.
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| 25. |
- Haslam, Danielle E., et al.
(author)
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Changes in metabolites during an oral glucose tolerance test in early and mid-pregnancy : Findings from the PEARLS randomized, controlled lifestyle trial
- 2020
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In: Metabolites. - : MDPI AG. - 2218-1989. ; 10:7
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Journal article (peer-reviewed)abstract
- The oral glucose tolerance test (OGTT) is used to diagnose gestational and other types of diabetes. We examined metabolite changes during an OGTT, and how a comprehensive diet and physical activity intervention may influence these changes in a population of overweight/obese Hispanic pregnant women. Integration of changes in metabolites during an OGTT may help us gain preliminary insights into how glucose metabolism changes during pregnancy. Among women from the Pregnancy and EARly Lifestyle improvement Study (PEARLS), we measured metabolites during a multipoint OGTT (fasting, 30, 60 and 120 min) at early and mid-pregnancy. Metabolite levels were measured by liquid chromatography–mass spectrometry in plasma samples in the lifestyle intervention (n = 13) and control (n = 16) arms of the study. A total of 65 candidate metabolites were selected that displayed changes during an OGTT in previous studies. Paired and unpaired t-tests were used to examine differences in ∆fast-120 min: (1) at early and mid-pregnancy; and (2) by intervention assignment. We applied principal component analysis (PCA) to identify those metabolites that differed by intervention assignment and OGTT time points. Most of the characteristic changes in metabolites post-OGTT were similar at both gestational time points. PCA identified characteristic metabolite patterns associated with OGTT time points at both early and mid-pregnancy. These metabolites included ketone bodies, tryptophan, acyl carnitines, polyunsaturated fatty acids, and biomarkers related to bile acid, urea cycle, arginine, and proline metabolism. PCA identified distinct ∆fast-120 min in fatty acid, acyl carnitine, bile acid, ketone body, and amino acid levels at mid-compared to early pregnancy. Participants in the intervention group did not display mean decreases in ∆fast-120 min of several long-chain acyl carnitines that were observed in the control group. These findings provide preliminary insight into metabolites, whose role in increased insulin resistance during pregnancy, should be explored further in future studies.
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