| 1. |
- Shu, Xiang, et al.
(författare)
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Large-scale Integrated Analysis of Genetics and Metabolomic Data Reveals Potential Links Between Lipids and Colorectal Cancer Risk
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:6, s. 1216-1226
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Tidskriftsartikel (refereegranskat)abstract
- Background: The etiology of colorectal cancer is not fully understood.Methods: Using genetic variants and metabolomics data including 217 metabolites from the Framingham Heart Study (n = 1,357), we built genetic prediction models for circulating metabolites. Models with prediction R2 > 0.01 (Nmetabolite = 58) were applied to predict levels of metabolites in two large consortia with a combined sample size of approximately 46,300 cases and 59,200 controls of European and approximately 21,700 cases and 47,400 controls of East Asian (EA) descent. Genetically predicted levels of metabolites were evaluated for their associations with colorectal cancer risk in logistic regressions within each racial group, after which the results were combined by meta-analysis.Results: Of the 58 metabolites tested, 24 metabolites were significantly associated with colorectal cancer risk [Benjamini-Hochberg FDR (BH-FDR) < 0.05] in the European population (ORs ranged from 0.91 to 1.06; P values ranged from 0.02 to 6.4 × 10-8). Twenty one of the 24 associations were replicated in the EA population (ORs ranged from 0.26 to 1.69, BH-FDR < 0.05). In addition, the genetically predicted levels of C16:0 cholesteryl ester was significantly associated with colorectal cancer risk in the EA population only (OREA: 1.94, 95% CI, 1.60−2.36, P = 2.6 × 10-11; OREUR: 1.01, 95% CI, 0.99−1.04, P = 0.3). Nineteen of the 25 metabolites were glycerophospholipids and triacylglycerols (TAG). Eighteen associations exhibited significant heterogeneity between the two racial groups (PEUR-EA-Het < 0.005), which were more strongly associated in the EA population. This integrative study suggested a potential role of lipids, especially certain glycerophospholipids and TAGs, in the etiology of colorectal cancer.Conclusions: This study identified potential novel risk biomarkers for colorectal cancer by integrating genetics and circulating metabolomics data.Impact: The identified metabolites could be developed into new tools for risk assessment of colorectal cancer in both European and EA populations.
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| 2. |
- Hyun, Gyu Hwan, et al.
(författare)
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Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity
- 2023
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 17:12, s. 11567-11582
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Tidskriftsartikel (refereegranskat)abstract
- Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation. Gal-NC is characterized as a carbohydrate nanoadjuvant with a macrophage-targeting feature. It is composed of repeating galactan glycopatterns derived from heteropolysaccharide structures of plant origin. The galactan repeats of Gal-NC function as multivalent pattern-recognition sites for Toll-like receptor 4 (TLR4). Functionally, Gal-NC-mediated TLR activation induces the repolarization of tumor-associated macrophages (TAMs) toward immunostimulatory/tumoricidal M1-like phenotypes. Gal-NC increases the intratumoral population of cytotoxic T cells, the main effector cells of antitumor immunity, via re-educated TAMs. These TME alterations synergistically enhance the T-cell-mediated antitumor response induced by αPD-1 administration, suggesting that Gal-NC has potential value as an adjuvant for immune checkpoint blockade combination therapies. Thus, the Gal-NC model established herein suggests a glycoengineering strategy to design a carbohydrate-based nanocomposite for advanced cancer immunotherapies.
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| 3. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Abolfathi, Bela, et al.
(författare)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Tidskriftsartikel (refereegranskat)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 5. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 6. |
- Cai, Liangliang, et al.
(författare)
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Direct Formation of C-C Double-Bonded Structural Motifs by On-Surface Dehalogenative Homocoupling of gem-Dibromomethyl Molecules
- 2018
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Ingår i: ACS Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 12:8, s. 7959-7966
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Tidskriftsartikel (refereegranskat)abstract
- Conductive polymers are of great importance in a variety of chemistry-related disciplines and applications. The recently developed bottom-up on-surface synthesis strategy provides us with opportunities for the fabrication of various nanostructures in a flexible and facile manner, which could be investigated by high-resolution microscopic techniques in real space. Herein, we designed and synthesized molecular precursors functionalized with benzal gem-dibromomethyl groups. A combination of scanning tunneling microscopy, noncontact atomic force microscopy, high-resolution synchrotron radiation photoemission spectroscopy, and density functional theory calculations demonstrated that it is feasible to achieve the direct formation of C-C double-bonded structural motifs via on-surface dehalogenative homocoupling reactions on the Au(111) surface. Correspondingly, we convert the sp(3)-hybridized state to an sp(2)-hybridized state of carbon atoms, i.e., from an alkyl group to an alkenyl one. Moreover, by such a bottom-up strategy, we have successfully fabricated poly(phenylenevinylene) chains on the surface, which is anticipated to inspire further studies toward understanding the nature of conductive polymers at the atomic scale.
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| 7. |
- Chang, Keke, et al.
(författare)
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Considerations on Circuit Design and Data Acquisition of a Portable Surface Plasmon Resonance Biosensing System
- 2015
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Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 15:8, s. 20511-20523
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop a circuit for an inexpensive portable biosensing system based on surface plasmon resonance spectroscopy. This portable biosensing system designed for field use is characterized by a special structure which consists of a microfluidic cell incorporating a right angle prism functionalized with a biomolecular identification membrane, a laser line generator and a data acquisition circuit board. The data structure, data memory capacity and a line charge-coupled device (CCD) array with a driving circuit for collecting the photoelectric signals are intensively focused on and the high performance analog-to-digital (A/D) converter is comprehensively evaluated. The interface circuit and the photoelectric signal amplifier circuit are first studied to obtain the weak signals from the line CCD array in this experiment. Quantitative measurements for validating the sensitivity of the biosensing system were implemented using ethanol solutions of various concentrations indicated by volume fractions of 5%, 8%, 15%, 20%, 25%, and 30%, respectively, without a biomembrane immobilized on the surface of the SPR sensor. The experiments demonstrated that it is possible to detect a change in the refractive index of an ethanol solution with a sensitivity of 4.99838 × 10(5) ΔRU/RI in terms of the changes in delta response unit with refractive index using this SPR biosensing system, whereby the theoretical limit of detection of 3.3537 × 10(-5) refractive index unit (RIU) and a high linearity at the correlation coefficient of 0.98065. The results obtained from a series of tests confirmed the practicality of this cost-effective portable SPR biosensing system.
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| 8. |
- Heald, G., et al.
(författare)
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Magnetism science with the square kilometre array
- 2020
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Ingår i: Galaxies. - : MDPI AG. - 2075-4434. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- The Square Kilometre Array (SKA) will answer fundamental questions about the origin, evolution, properties, and influence of magnetic fields throughout the Universe. Magnetic fields can illuminate and influence phenomena as diverse as star formation, galactic dynamics, fast radio bursts, active galactic nuclei, large-scale structure, and dark matter annihilation. Preparations for the SKA are swiftly continuing worldwide, and the community is making tremendous observational progress in the field of cosmic magnetism using data from a powerful international suite of SKA pathfinder and precursor telescopes. In this contribution, we revisit community plans for magnetism research using the SKA, in light of these recent rapid developments. We focus in particular on the impact that new radio telescope instrumentation is generating, thus advancing our understanding of key SKA magnetism science areas, as well as the new techniques that are required for processing and interpreting the data. We discuss these recent developments in the context of the ultimate scientific goals for the SKA era.
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| 9. |
- Ji, Xiang, et al.
(författare)
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Dissemination of extended-spectrum beta-lactamase-producing Escherichia coli carrying mcr-1 among multiple environmental sources in rural China and associated risk to human health
- 2019
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Ingår i: Environmental Pollution. - : ELSEVIER SCI LTD. - 0269-7491 .- 1873-6424. ; 251, s. 619-627
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance among gram-negative bacteria is increasingly becoming a problem of global concern. Particularly problematic is the emergence of resistance to last-resort antibiotics such as carbapenems and colistin. The increasing number of reports on the plasmid-mediated colistin resistance gene mcr-1 in isolates worldwide is raising concerns for the future usefulness of this class of antibiotics. Dissemination of mcr-1 is believed to have originated mainly from animal breeding, however, the role of the environment as a transmission source is not yet fully understood. In the current study, 89 extended spectrum beta-lactamase-producing Escherichia coli isolated from 231 samples from different environmental sources in 12 villages in a rural area of Shandong, China, were screened for mcr-1.17 (19.1%) mcr-1-positive isolates were found from different environmental sources, aggregated in 6 villages. Plasmids of three different Inc-groups carrying mcr-1 were confirmed, indicating that the widespread geographical distribution of mcr-1 in the local area is due to a number of different plasmids. Additionally, almost a third (29.4%) of the isolates carried virulence factors associated to intestinal pathogenic E. coli. These results illustrate the high complexity of the transmission patterns of mcr-1 among different environmental matrices on a local scale and the potential for the environment to facilitate dissemination and emergence of antibiotic-resistant and virulent strains of bacteria. (C) 2019 Elsevier Ltd. All rights reserved.
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| 10. |
- Li, Yongqiang, et al.
(författare)
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Activation of locally excavated spoil for utilization in limestone calcined clay cement (LC3)
- 2024
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Ingår i: Construction and Building Materials. - 0950-0618. ; 420
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Tidskriftsartikel (refereegranskat)abstract
- The utilization of clay to produce limestone calcined clay cement (LC3) is limited in China due to environmental concerns related to clay excavation. This study explores the potential to activate the fine-grained clay sourced from excavated spoil in Shenzhen, China for LC3 production. A water washing method was introduced to treat the excavated spoil, enriching the clays’ kaolinite content in a range of 72.4–83.1%. Incorporation of calcined clay with different calcination procedures will modify the hydration rate for aluminate, and the longer calcination after 2 h is detrimental for clay reactivity. Additionally, using excavated spoil calcined at 800 °C with more than 2 h in paste yields compressive strength comparable to that of paste made of ordinary Portland cement (OPC). Calcining at 800 °C for 2 h is the optimal calcination procedure to activate the collected soil. Notably, this activation approach for LC3 production exhibits remarkable environmental and economic benefits, reinforcing the potential for extensive adoption of LC3 within China.
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