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- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 3. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 10. |
- Huo, X. M., et al.
(författare)
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Parameterized inverse kinematics of parallel mechanism based on CGA
- 2019
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Ingår i: EuCoMeS 2018 Proceedings of the 7th European Conference on Mechanism Science. - Cham : Springer Netherlands. ; , s. 340-346
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Konferensbidrag (refereegranskat)abstract
- A parameterized inverse kinematic model is the theoretical basis for performance analysis, design and control of parallel mechanism (PM). Current methods are either computationally expensive or difficult to get analytical form. To deal with this problem, this paper proposes a parameterized method by conformal geometric algebra (CGA). Based on the description and computation of screw motions in CGA, closure equations about successive screw displacements of any PM can be formulated. Joint displacements of each limb and screw parameters of end-effector are then solved in an analytical manner. The proposed method is exemplified by a 3 degree-of-freedom (DoF) PM, which shows high efficiency in deriving the analytical inverse kinematic model.
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| 11. |
- Li, J. W., et al.
(författare)
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Magnetocaloric effect in heavy rare-earth elements doped Fe-based bulk metallic glasses with tunable Curie temperature
- 2014
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 116:6, s. Art. no. 063902-
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Tidskriftsartikel (refereegranskat)abstract
- The effects of heavy rare earth (RE) additions on the Curie temperature (T-C) and magnetocaloric effect of the Fe-RE-B-Nb (RE-Gd, Dy and Ho) bulk metallic glasses were studied. The type of dopping RE element and its concentration can easily tune T-C in a large temperature range of 120K without significantly decreasing the magnetic entropy change (Delta S-M) and refrigerant capacity (RC) of the alloys. The observed values of Delta S-M and RC of these alloys compare favorably with those of recently reported Fe-based metallic glasses with enhanced RC compared to Gd5Ge1.9Si2Fe0.1. The tunable T-C and large glass-forming ability of these RE doped Fe-based bulk metallic glasses can be used in a wide temperature range with the final required shapes.
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| 15. |
- Xiong, K., et al.
(författare)
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From spin coating to doctor blading: A systematic study on the photovoltaic performance of an isoindigo-based polymer
- 2015
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Ingår i: Solar Energy Materials and Solar Cells. - : Elsevier BV. - 0927-0248. ; 132, s. 252-259
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Tidskriftsartikel (refereegranskat)abstract
- Doctor blading is suitable to roll-to-roll process with much little solution wasting and is less studied compared with the mainstream spin coating. In this work, we used a novel polymer blended with two common fullerene derivatives as active solutions. To systemically understand the different coating methods and the different fullerene acceptors on the effect of polymer solar cells (PSCs) photovoltaic performance, the wet active solution physic-chemical properties and variations of the dried active layer characterizations were investigated. It was observed that it is much easier to obtain a homogeneous film from doctor blading compared with spin coating for the polymer: PC71BM solution due to the high surface tension and viscosity. Moreover, the high boiling point additive plays an important role in inhibiting the wet film shrinkage and forming a uniform film. The longer film drying time for the doctor-blading films leads to larger domains than spin coating, thus increases the geminate recombination and results in lower mobilities as well as power conversion efficiencies (PCE). Doctor-blading-processed PSCs with PCE of 4.46% were achieved for P3TI:PC71BM devices, which were comparable to those of spin-coating devices. This work provided valuable suggestions and solutions for the doctor-blading process, especially for crystalline D-A polymer-based devices.
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| 16. |
- Yu, Ling-Zhu, et al.
(författare)
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MEK1/2 regulates microtubule organization, spindle pole tethering and asymmetric division during mouse oocyte meiotic maturation.
- 2007
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Ingår i: Cell cycle (Georgetown, Tex.). - 1551-4005. ; 6:3, s. 330-8
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that MAPK plays pivotal roles in oocyte maturation, but the function of MEK (MAPK kinase) remains unknown. We have studied the expression, subcellular localization and functional roles of MEK during meiotic maturation of mouse oocytes. Firstly, we found that MEK1/2 phoshorylation (p-MEK1/2, indicative of MEK activation) was low in GV (germinal vesicle) stage, increased 2h after GVBD (germinal vesicle breakdown), and reached the maximum at metaphase II. Secondly, we found that P-MEK1/2 was restricted in the GV prior to GVBD. In prometaphase I and metaphase I, P-MEK1/2 was mainly associated with the spindle, especially with the spindle poles. At anaphase I and telophase I, p-MEK1/2 became diffusely distributed in the region between the separating chromosomes, and then became associated with the midbody. The association of p-MEK1/2 with spindle poles was further confirmed by its colocalization with the centrosomal proteins, gamma-tubulin and NuMA. Thirdly, we have investigated the possible functional role of MEK1/2 activation by intravenous administration and intrabursal injection of a specific MEK inhibitor, U0126, and by microinjection of MEK siRNA into oocytes. All these manipulations cause disorganized spindle poles and spindle structure, misaligned chromosomes and larger than normal polar bodies. Our results suggest that MEK1/2 may function as a centrosomal protein and may have roles in microtubule organization, spindle pole tethering and asymmetric division during mouse oocyte maturation.
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