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| 2. |
- 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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| 3. |
- 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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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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- 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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- Vaikath, Nishant Narayanan, et al.
(författare)
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Generation and characterization of novel conformation-specific monoclonal antibodies for α-synuclein pathology.
- 2015
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 79, s. 81-99
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Tidskriftsartikel (refereegranskat)abstract
- α-Synuclein (α-syn), a small protein that has the intrinsic propensity to aggregate, is implicated in several neurodegenerative diseases including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), which are collectively known as synucleinopathies. Genetic, pathological, biochemical, and animal modeling studies provided compelling evidence that α-syn aggregation plays a key role in the pathogenesis of PD and related synucleinopathies. It is therefore of utmost importance to develop reliable tools that can detect the aggregated forms of α-syn. We describe here the generation and characterization of six novel conformation-specific monoclonal antibodies that recognize specifically α-syn aggregates but not the soluble, monomeric form of the protein. The antibodies described herein did not recognize monomers or fibrils generated from other amyloidogenic proteins including β-syn, γ-syn, β-amyloid, tau protein, islet amyloid polypeptide and ABri. Interestingly, the antibodies did not react to overlapping linear peptides spanning the entire sequence of α-syn, confirming further that they only detect α-syn aggregates. In immunohistochemical studies, the new conformation-specific monoclonal antibodies showed underappreciated small micro-aggregates and very thin neurites in PD and DLB cases that were not observed with generic pan antibodies that recognize linear epitope. Furthermore, employing one of our conformation-specific antibodies in a sandwich based ELISA, we observed an increase in levels of α-syn oligomers in brain lysates from DLB compared to Alzheimer's disease and control samples. Therefore, the conformation-specific antibodies portrayed herein represent useful tools for research, biomarkers development, diagnosis and even immunotherapy for PD and related pathologies.
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