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| 3. |
- Kim, Kwangwoo, et al.
(författare)
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High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case-control samples. Results We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5x10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusions This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
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- Lee, Seung Joon, et al.
(författare)
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Microslit on a chip: A simplified filter to capture circulating tumor cells enlarged with microbeads
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Microchips are widely used to separate circulating tumor cells (CTCs) from whole blood by virtues of sophisticated manipulation for microparticles. Here, we present a chip with an 8 µm high and 27.9 mm wide slit to capture cancer cells bound to 3 µm beads. Apart from a higher purity and recovery rate, the slit design allows for simplified fabrication, easy cell imaging, less clogging, lower chamber pressure and, therefore, higher throughput. The beads were conjugated with anti-epithelial cell adhesion molecules (anti-EpCAM) to selectively bind to breast cancer cells (MCF-7) used to spike the whole blood. The diameter of the cell-bead construct was in average 23.1 µm, making them separable from other cells in the blood. As a result, the cancer cells were separated from 5 mL of whole blood with a purity of 52.0% and a recovery rate of 91.1%, and also we confirmed that the device can be applicable to clinical samples of human breast cancer patients. The simple design with microslit, by eliminating any high-aspect ratio features, is expected to reduce possible defects on the chip and, therefore, more suitable for mass production without false separation outputs.
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- Shvartzvald, Yossi, et al.
(författare)
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Spitzer Microlensing Parallax for OGLE-2017-BLG-0896 Reveals a Counter-rotating Low-mass Brown Dwarf
- 2019
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 157:3
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Tidskriftsartikel (refereegranskat)abstract
- The kinematics of isolated brown dwarfs in the Galaxy, beyond the solar neighborhood, is virtually unknown. Microlensing has the potential to probe this hidden population, as it can measure both the mass and five of the six phase-space coordinates (all except the radial velocity) even of a dark isolated lens. However, the measurements of both the microlens-parallax and finite-source effects are needed in order to recover the full information. Here, we combine the Spitzer satellite parallax measurement with the ground-based light curve, which exhibits strong finite-source effects, of event OGLE-2017-BLG-0896. We find two degenerate solutions for the lens (due to the known satellite-parallax degeneracy), which are consistent with each other except for their proper motion. The lens is an isolated brown dwarf with a mass of either 18 +/- 1 M-J or 20 +/- 1 M-J. This is the lowest isolated-object mass measurement to date, only similar to 45% more massive than the theoretical deuterium-fusion boundary at solar metallicity, which is the common definition of a free-floating planet. The brown dwarf is located at either 3.9 +/- 0.1 kpc or 4.1 +/- 0.1 kpc toward the Galactic bulge, but with proper motion in the opposite direction of disk stars, with one solution suggesting it is moving within the Galactic plane. While it is possibly a halo brown dwarf, it might also represent a different, unknown population.
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- Shin, Hyun Young, et al.
(författare)
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Cell Seeding Technology for Microarray-Based Quantitative Human Primary Skeletal Muscle Cell Analysis
- 2019
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Ingår i: Analytical Chemistry. - : AMER CHEMICAL SOC. - 0003-2700 .- 1520-6882. ; 91:22, s. 14214-14219
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Tidskriftsartikel (refereegranskat)abstract
- Pipetting techniques play a crucial role in obtaining reproducible and reliable results, especially when seeding cells on small target areas, such as on microarrays, biochips or microfabricated cell culture systems. For very rare cells, such as human primary skeletal muscle cells (skMCs), manual (freehand) cell seeding techniques invariably result in nonuniform cell spreading and heterogeneous cell densities, giving rise to undesirable variations in myogenesis and differentiation. To prevent such technique-dependent variation, we have designed and fabricated a simple, low-cost pipet guidance device (PGD), and holder that works with hand-held pipettes. This work validates the accuracy and reproducibility of the PGD platform and compares its effectiveness with manual and robotic seeding techniques. The PGD system ensures reproducibility of cell seeding, comparable to that of more expensive robotic dispensing systems, resulting in a high degree of cell uniformity and homogeneous cell densities, while also enabling cell community studies. As compared to freehand pipetting, PGD-assisted seeding of C2C12 mouse myoblasts showed 5.3 times more myotube formation and likewise myotubes derived from PGD-seeded human primary skMCs were 3.6 times thicker and 2.2 times longer. These results show that this novel, yet simple PGD-assisted pipetting technique provides precise cell seeding on small targets, ensuring reproducible and reliable high-throughput cell assays.
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- Yang, Seung Won, et al.
(författare)
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Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation
- 2018
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Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 32:5, s. 2658-2675
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Tidskriftsartikel (refereegranskat)abstract
- A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins. The RNA as a molecular chaperone (chaperna) activity is intrinsic to some ribozymes and is operational during viral infections. Our purpose was to test whether influenza hemagglutinin (HA) can be assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity. An RNA-interacting domain (RID) from the host being immunized was selected as a docking tag for RNA binding, which served as a transducer for the chaperna function for de novo folding and trimeric assembly of RID-HA1. Mutations that affect tRNA binding greatly increased the soluble aggregation defective in trimer assembly, suggesting that RNA interaction critically controls the kinetic network in the folding/assembly pathway. Immunization of mice resulted in strong hemagglutination inhibition and high titers of a neutralizing antibody, providing sterile protection against a lethal challenge and confirming the immunologically relevant HA conformation. The results may be translated into a rapid response to a new influenza pandemic. The harnessing of the novel chaperna described herein with immunologically tailored antigen-folding functions should serve as a robust prophylactic and diagnostic tool for viral infections.
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- Lee, Seung Jae, et al.
(författare)
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Robust Acceleration Control of a Hexarotor UAV with a Disturbance Observer
- 2016
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Ingår i: 2016 IEEE 55th Conference on Decision and Control, CDC 2016. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781509018376 ; , s. 4166-4171
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Konferensbidrag (refereegranskat)abstract
- This paper presents an acceleration control of a hexarotor unmanned aerial vehicle (UAV) in the earth fixed frame with a disturbance observer (DOB). Unlike conventional cascade control structures where the outer-loop position controller generates the desired attitude command, the position controller in this paper generates the desired acceleration command in X, V. Z axis of the earth-fixed frame. With acceleration control combined with DOB, the UAV could manage the lateral disturbance force that makes the trajectory tracking very challenging. This is a new concept compared with existing DOB-based UAV control approaches which aim to cancel the moment disturbance for precise attitude control. The small-gain theorem is used for stability analysis and Q-filter bandwidth design. Both simulation and actual experiment are shown to validate the performance of the proposed design.
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- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 10. |
- Lee, Seung Jae, et al.
(författare)
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Design, Modeling and Control of T-3-Multirotor : a Tilting Thruster Type Multirotor
- 2018
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Ingår i: 2018 IEEE INTERNATIONAL CONFERENCE ON ROBOTICS AND AUTOMATION (ICRA). - : IEEE Computer Society. - 9781538630815 ; , s. 1214-1219
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Konferensbidrag (refereegranskat)abstract
- This paper presents a new design of multirotor, named as 'Tilting Thruster Type' (T-3)-multirotor. The new platform is equipped with mechanically separated thrusters, which can take any fuselage posture within a specified range regardless of any direction of translational acceleration. A specially designed servo-linkage mechanism is employed for relative attitude control between the thruster and the fuselage. Mathematical modeling and analysis of the new platform are conducted to explore the control method of the dynamically complex system. For demonstrating the potential of the new T(3-)multirotor, an autonomous level flight is performed where the fuselage maintains zero roll and pitch angle during the entire flight. Both simulation and experimental results are provided with detailed analysis.
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