| 1. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
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.
|
|
| 2. |
- Abolfathi, Bela, et al.
(författare)
-
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
-
Ingår i: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
-
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.
|
|
| 3. |
- Cai, Liangliang, et al.
(författare)
-
Direct Formation of C-C Double-Bonded Structural Motifs by On-Surface Dehalogenative Homocoupling of gem-Dibromomethyl Molecules
- 2018
-
Ingår i: ACS Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 12:8, s. 7959-7966
-
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.
|
|
| 4. |
- Cao, Zi-Jun, et al.
(författare)
-
State-of-the-art review of inherent variability and uncertainty in geotechnical properties and models : Chapter 6: Determining characteristic values of geotechnical parameters and resistance: an overview
- 2021
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- CEN committee TC250 is currently working on an update of the Eurocodes. Subcommittee SC10,in charge of updating EN 1990 (Basis of structural and geotechnical design has installed aworking group to produce a background document with the working title ‘Reliability Backgrounds of the Eurocodes’, with the intention to document and explain the reliability framework underlying all Eurocodes and the implementation of reliability aspects in them. As part of that effort, quantitative information on the inherent variability and uncertainty in loads, material properties and models is compiled. ISSMGE TC304 identified this as an opportunity to provide an overview of the relevant information available in the geotechnical literature such as the statistics of soil/rock properties. The EPRI TR 105000 report (Phoon et al. 1995) provided an overview of the statistics of inherent soil properties and measurement errors, but these statistics have not yet been updated systematically since 1995. Also, rock properties were not covered by the TR 105000 report. Other than soil/rock properties and measurement errors, there are also other important statistics, such as the statistics of transformation uncertainties and model factors.The current technical report has the following features:1. It serves as an update for the TR 105000 report on the statistics of inherent soil properties. Chapter 1 compiles the site specific statistics for univariate soil properties. Chapter 3 compiles the random field parameters (e.g., the scales of fluctuation) for spatial variability of soils. Many of the statistics are new.2. It contains statistics that are not covered by the TR 105000 report. Chapter 1 compiles the site specific statistics for some rock and rock mass properties. Chapter 2 compiles the site specific correlations between soil/rock properties. Chapter 5 compiles the statistics for transformation uncertainties.3. Chapter 4 compiles the statistics of geotechnical design model factors . Chapter 6 reviews methods that determine the characteristic value defined by the Eurocode 7. Chapter 7 reviews some numerical evidences for the worst case scale of fluctuation.
|
|
| 5. |
- Chen, Jian, et al.
(författare)
-
Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects
- 2017
-
Ingår i: Emerging Microbes & Infections. - : NATURE PUBLISHING GROUP. - 2222-1751. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Zika virus (ZIKV) infection can cause fetal developmental abnormalities and Guillain-Barre syndrome in adults. Although progress has been made in understanding the link between ZIKV infection and microcephaly, the pathology of ZIKV, particularly the viral reservoirs in human, remains poorly understood. Several studies have shown that compared to serum samples, patients' urine samples often have a longer duration of ZIKV persistency and higher viral load. This finding suggests that an independent viral reservoir may exist in the human urinary system. Despite the clinical observations, the host cells of ZIKV in the human urinary system are poorly characterized. In this study, we demonstrate that ZIKV can infect renal proximal tubular epithelial cells (RPTEpiCs) in immunodeficient mice in vivo and in both immortalized and primary human renal proximal tubular epithelial cells (hRPTEpiCs) in vitro. Importantly, ZIKV infection in mouse kidneys caused caspase-3-mediated apoptosis of renal cells. Similarly, in vitro infection of immortalized and primary hRPTEpiCs resulted in notable cytopathic effects. Consistent with the clinical observations, we found that ZIKV infection can persist with prolonged duration in hRPTEpiCs. RNA-Seq analyses of infected hRPTEpiCs revealed a large number of transcriptional changes in response to ZIKV infection, including type I interferon signaling genes and anti-viral response genes. Our results suggest that hRPTEpiCs are a potential reservoir of ZIKV in the human urinary system, providing a possible explanation for the prolonged persistency of ZIKV in patients' urine.
|
|
| 6. |
- Hyun, Gyu Hwan, et al.
(författare)
-
Multivalent Carbohydrate Nanocomposites for Tumor Microenvironment Remodeling to Enhance Antitumor Immunity
- 2023
-
Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 17:12, s. 11567-11582
-
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.
|
|
| 7. |
- Jin, Bao, et al.
(författare)
-
Phase transition structural superlubricity
- 2024
-
Ingår i: Matter. - : Cell Press. - 2590-2393 .- 2590-2385.
-
Tidskriftsartikel (refereegranskat)abstract
- Structural superlubricity refers to a state with almost vanishing friction and wear between crystalline surfaces in incommensurate configurations. However, thus far, this phenomenon has been observed only at solid-solid interfaces. Here, we constructed an in situ heterojunction between a crystalline boundary tribofilm and a pressure-induced solid-phase 1–dodecanol molecular layer, achieving structural superlubricity in a liquid-solid interface. This novel superlubricity state, termed phase transition structural superlubricity (PTSS), is induced by incommensurate slip at the in situ heterojunction. Atomic force microscopy experiments and molecular dynamics simulations demonstrated that the friction of in situ heterojunction exhibits a periodicity of 180°. Notably, the PTSS arises when the molecular axis of 1–dodecanol is oriented 90° to the direction of friction. These findings provide a novel design strategy for structural superlubricity and bridge the gap between liquid and solid superlubricity, shedding substantial light upon achieving structural superlubricity across a broad range of environments.
|
|
| 8. |
- Lindblad-Toh, Kerstin, et al.
(författare)
-
Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
|
|
| 9. |
- Wang, Jinling, et al.
(författare)
-
Bcl-2 hijacks the arsenic trioxide resistance in SH-SY5Y cells
- 2022
-
Ingår i: Journal of Cellular and Molecular Medicine. - : Wiley. - 1582-1838 .- 1582-4934. ; 26:2, s. 563-569
-
Tidskriftsartikel (refereegranskat)abstract
- Aresenic trioxide (ATO) is proven to be active against leukaemia cells by inducing apoptosis and differentiation. Even though ATO could effectively induce remissions of leukaemia cells, the drug resistance was observed occasionally. To further dissect the mechanism of ATO resistance, we selected the ATO-resistant SH-SY5Y cells and found that Bcl-2 controlled the sensitivity of ATO in SH-SY5Y cells. We report that necroptosis, autophagy, NF-ƘB and MAPK signalling pathway are not involved in ATO-induced apoptosis. Moreover, the ATO-resistant cells showed distinct mitochondrial morphology compared with that of ATO-sensitive cells. Intriguingly, nude mice-bearing ATO-sensitive cells derived xenograft tumours are more sensitive to ATO treatment compared with that of ATO-resistant cells. These data demonstrate that cancer cells can acquire the ATO-resistance ability by increasing the Bcl-2 expression.
|
|
| 10. |
- Yu, L., et al.
(författare)
-
Multi-layer mucilage of Plantago ovata seeds : Rheological differences arise from variations in arabinoxylan side chains
- 2017
-
Ingår i: Carbohydrate Polymers. - : Elsevier Ltd. - 0144-8617 .- 1879-1344. ; 165, s. 132-141
-
Tidskriftsartikel (refereegranskat)abstract
- Mucilages are hydrocolloid solutions produced by plants for a variety of functions, including the creation of a water-holding barrier around seeds. Here we report our discovery of the formation of three distinct mucilage layers around Plantago ovata seeds upon their hydration. Each layer is dominated by different arabinoxylans (AXs). These AXs are unusual because they are highly branched and contain β-1,3-linked xylose in their side chains. We show that these AXs have similar monosaccharide and linkage composition, but vary in their polymer conformation. They also exhibit distinct rheological properties in aqueous solution, despite analytical techniques including NMR showing little difference between them. Using enzymatic hydrolysis and chaotropic solvents, we reveal that hydrogen bonding and side chain distribution are key factors underpinning the distinct rheological properties of these complex AXs.
|
|
| 11. |
- Yu, Xiao, et al.
(författare)
-
Improving Ranking-Oriented Defect Prediction Using a Cost-Sensitive Ranking SVM
- 2020
-
Ingår i: IEEE Transactions on Reliability. - : Institute of Electrical and Electronics Engineers Inc.. - 0018-9529 .- 1558-1721. ; 69:1, s. 139-153
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Ranking-oriented defect prediction (RODP) ranks software modules to allocate limited testing resources to each module according to the predicted number of defects. Most RODP methods overlook that ranking a module with more defects incorrectly makes it difficult to successfully find all of the defects in the module due to fewer testing resources being allocated to the module, which results in much higher costs than incorrectly ranking the modules with fewer defects, and the numbers of defects in software modules are highly imbalanced in defective software datasets. Cost-sensitive learning is an effective technique in handling the cost issue and data imbalance problem for software defect prediction. However, the effectiveness of cost-sensitive learning has not been investigated in RODP models. Aims: In this article, we propose a cost-sensitive ranking support vector machine (SVM) (CSRankSVM) algorithm to improve the performance of RODP models. Method: CSRankSVM modifies the loss function of the ranking SVM algorithm by adding two penalty parameters to address both the cost issue and the data imbalance problem. Additionally, the loss function of the CSRankSVM is optimized using a genetic algorithm. Results: The experimental results for 11 project datasets with 41 releases show that CSRankSVM achieves 1.12%-15.68% higher average fault percentile average (FPA) values than the five existing RODP methods (i.e., decision tree regression, linear regression, Bayesian ridge regression, ranking SVM, and learning-to-rank (LTR)) and 1.08%-15.74% higher average FPA values than the four data imbalance learning methods (i.e., random undersampling and a synthetic minority oversampling technique; two data resampling methods; RankBoost, an ensemble learning method; IRSVM, a CSRankSVM method for information retrieval). Conclusion: CSRankSVM is capable of handling the cost issue and data imbalance problem in RODP methods and achieves better performance. Therefore, CSRankSVM is recommended as an effective method for RODP. © 1963-2012 IEEE.
|
|
