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| 2. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 3. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 4. |
- Geng, Xiaofei, et al.
(författare)
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Year-Round Measurements of Dissolved Black Carbon in Coastal Southeast Asia Aerosols : Rethinking Its Atmospheric Deposition in the Ocean
- 2021
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 126:18
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Tidskriftsartikel (refereegranskat)abstract
- Dissolved black carbon (DBC) is an important recalcitrant fraction of marine dissolved organic matter. Riverine discharge is the largest known source of oceanic DBC; however, the significance of atmospheric deposition as a source of oceanic DBC remains poorly understood. In this study, year-round aerosol sampling was carried out at a rural coastal site in Southeast Asia for DBC analysis using the benzene polycarboxylic acid (BPCA) method. The results revealed the uncertainty of an earlier estimate of the atmospheric deposition flux of DBC to the global ocean (FDBC), which assumed a linear correlation between DBC and water-soluble organic carbon (WSOC). The correlation between DBC and WSOC depended on the sources of carbonaceous aerosols. The DBC/WSOC ratios were higher for the biomass burning aerosols. DBC was linearly correlated with black carbon (BC) for biomass or fossil fuel combustion aerosols. However, the DBC/BC ratios were higher for biomass burning aerosols (0.41 ± 0.22), whereas lower for fossil fuel combustion aerosols (0.04 ± 0.03). FDBC was revisited based on the relationship between DBC and BC. FDBC is primarily contributed by biomass burning aerosols and maybe previously underestimated. In this study, the DBC in aerosols had less condensed aromatic structures than the DBC present in the major rivers of the world, as shown by the BPCA compositions. This indicated that oceanic DBC sourced from atmospheric deposition was less likely to be removed by photodegradation and sedimentation, as compared to the DBC sourced from riverine discharge.
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| 5. |
- Liu, Junwen, et al.
(författare)
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Isotope constraints of the strong influence of biomass burning to climate-forcing Black Carbon aerosols over Southeast Asia
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 744
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Tidskriftsartikel (refereegranskat)abstract
- Black Carbon (BC) deteriorates air quality and contributes to climate warming, yet its regionally- and seasonally-varying emission sources are poorly constrained. Here we employ natural abundance radiocarbon (C-14) measurements of BC intercepted at a northern Malaysia regional receptor site, Bachok, to quantify the relative biomass vs. fossil source contributions of atmospheric BC, in a first year-round study for SE Asia (December 2015-December 2016). The annual average C-14 signature suggests as large contributions from biomass burning as from fossil fuel combustion. This is similar to findings from analogous measurements at S Asian receptors sites (similar to 50% biomass burning), while E Asia sites are dominated by fossil emission (similar to 20% biomass burning). The C-14-based source fingerprinting of BC in the dry spring season in SE Asia signals an even more elevated biomass burning contribution (similar to 70% or even higher), presumably from forest, shrub and agricultural fires. This is consistent with this period showing also elevated ratio of organic carbon to BC (up from similar to 5 to 30) and estimates of BC emissions from satellite fire data. Hence, the present study emphasizes the importance of mitigating dry season vegetation fires in SE Asia.
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| 6. |
- Fan, Jin, et al.
(författare)
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Development of wideband orthomode transducers for FAST cryogenic receiver system
- 2020
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Ingår i: Research in Astronomy and Astrophysics. - : IOP Publishing. - 1674-4527. ; 20:5
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the design, construction, and performance of the wideband orthomode transducers (OMTs) for the L- (1.2-1.8 GHz), the S- (2-3 GHz) and the P- (0.56-1.12 GHz) band receiver systems of the Five-hundred-meter Aperture Spherical radio Telescope (FAST). These OMTs operate at the cryogenic temperature of 70K to reduce their thermal noise contribution to the receiver chains. The development on the FAST L- and S-band quad-ridged waveguide (QRWG) OMTs is carried out based on the theoretical mode analysis. In view of the miniaturization of FAST cryogenic receiver system at P-band, a novel wideband compact bowtie dipole OMT is designed with an octave bandwidth as well as a length of only quarter wavelength. The proposed L-, S- and P-band OMTs are designed and optimized by using Ansys High Frequency Structure Simulator (HFSS), and then manufactured, tested at room temperature. Measurement of FAST cryogenic receiver system noise is also performed with the L-, S- and P-band OMTs installed. The measured results fully comply with the design specifications.
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| 7. |
- Gan, Wensheng, et al.
(författare)
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Utility-Driven Data Analytics on Uncertain Data
- 2020
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Ingår i: IEEE Systems Journal. - : IEEE. - 1932-8184 .- 1937-9234. ; 14:3, s. 4442-4453
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Tidskriftsartikel (refereegranskat)abstract
- Modern Internet of Things (IoT) applications generate massive amounts of data, much of them in the form of objects/items of readings, events, and log entries. Specifically, most of the objects in these IoT data contain rich embedded information (e.g., frequency and uncertainty) and different levels of importance (e.g., unit risk/utility of items, interestingness, cost, or weight). Many existing approaches in data mining and analytics have limitations, such as only the binary attribute is considered within a transaction, as well as all the objects/items having equal weights or importance. To solve these drawbacks, a novel utility-driven data analytics algorithm named HUPNU is presented in this article. As a general utility-driven uncertain data mining model, HUPNU can extract High-Utility patterns by considering both Positive and Negative unit utilities from Uncertain data. The qualified high-utility patterns can be effectively discovered for intrusion detection, risk prediction, manufacturing management, and decision-making, among others. By using the developed vertical Probability-Utility list with the positive and negative utilities structure, as well as several effective pruning strategies, experiments showed that the developed HUPNU approach with the pruning strategies performed great in mining the qualified patterns efficiently and effectively.
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| 8. |
- Zhang, Yi, et al.
(författare)
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Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
- 2017
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 22:5
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Tidskriftsartikel (refereegranskat)abstract
- Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.
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