Identification of new SLE-associated genes with a two-step Bayesian study design

Armstrong, D L,Reiff, A,Myones, B L,Quismorio Jr, F P,Klein-Gitelman, M,McCurdy, D,Wagner-Weiner, L,Silverman, E,Ojwang, J O,Kaufman, K M,Kelly, J A,Merrill, J T,Harley, J B,Bae, S-C,Vyse, T J,Gilkeso Macmillan Publishers Limited 2009 GENES AND IMMUNITY Vol.10 No.5

In our earlier study, we utilized a Bayesian design to probe the association of ∼1000 genes (∼10 000 single-nucleotide polymorphisms (SNPs)) with systemic lupus erythematosus (SLE) on a moderate number of trios of parents and children with SLE. Two genes associated with SLE, with a multitest-corrected false discovery rate (FDR) of <0.05, were identified, and a number of noteworthy genes with FDR of <0.8 were also found, pointing out a future direction for the study. In this report, using a large population of controls and adult- or childhood-onset SLE cases, we have extended the earlier investigation to explore the SLE association of 10 of these noteworthy genes (109 SNPs). We have found that seven of these genes exhibit a significant (FDR<0.05) association with SLE, both confirming some genes that have earlier been found to be associated with SLE (PTPN22 and IRF5) and presenting novel findings of genes (KLRG1, interleukin-16, protein tyrosine phosphatase receptor type T, toll-like receptor (TLR)8 and CASP10), which have not been reported earlier. The results signify that the two-step candidate pathway design is an efficient way to study the genetic foundations of complex diseases. Furthermore, the novel genes identified in this study point to new directions in both the diagnosis and the eventual treatment of this debilitating disease.Genes and Immunity (2009) 10, 446–456; doi:10.1038/gene.2009.38; published online 14 May 2009

Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus.

Jacob, Chaim O,Zhu, Jiankun,Armstrong, Don L,Yan, Mei,Han, Jie,Zhou, Xin J,Thomas, James A,Reiff, Andreas,Myones, Barry L,Ojwang, Joshua O,Kaufman, Kenneth M,Klein-Gitelman, Marisa,McCurdy, Deborah,Wa National Academy of Sciences 2009 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.106 No.15

<P>A combined forward and reverse genetic approach was undertaken to test the candidacy of IRAK1 (interleukin-1 receptor associated kinase-1) as an X chromosome-encoded risk factor for systemic lupus erythematosus (SLE). In studying approximately 5,000 subjects and healthy controls, 5 SNPs spanning the IRAK1 gene showed disease association (P values reaching 10(-10), odds ratio >1.5) in both adult- and childhood-onset SLE, in 4 different ethnic groups, with a 4 SNP haplotype (GGGG) being strongly associated with the disease. The functional role of IRAK1 was next examined by using congenic mouse models bearing the disease loci: Sle1 or Sle3. IRAK1 deficiency abrogated all lupus-associated phenotypes, including IgM and IgG autoantibodies, lymphocytic activation, and renal disease in both models. In addition, the absence of IRAK1 reversed the dendritic cell 'hyperactivity' associated with Sle3. Collectively, the forward genetic studies in human SLE and the mechanistic studies in mouse models establish IRAK1 as a disease gene in lupus, capable of modulating at least 2 key checkpoints in disease development. This demonstration of an X chromosome gene as a disease susceptibility factor in human SLE raises the possibility that the gender difference in SLE may in part be attributed to sex chromosome genes.</P>

微量分析의 取扱法

朴冕用 건국대학교 1973 文理論叢 Vol.2 No.1

ppm∼ppb 범위의 무기 혹은 유기분석에서 용액의 취급방법은 보정과 검출한계성에 중요한 역활을 한다. 몇개의 참고 문헌을 이용하여 미량분석에 수반되는 오차와 시료(試料)의 녹임에 대하여 검토하였다. L'auteur passe en revue, quelques publications traitant de me´thodes de pre´paration et de dissolution d'e´chantillons a l'etat de traces avant leur dosage. Les erreurs dans ces me´thodes, rendues plus difficiles a´ re´duire a´ cause des operations supplementaires exige´es, sont compare´es a´ celles associe´es aux methodes plus directes. Dans le dosage d'e´lements au niveau de la ppb dens les matrices mine´rales et organigues, les techniques en solution sont utiles parce qu'elles simplifient les proble´mes d'etalonnage et ame´liorent la limite de de´tection.

Marx의 인간관 연구

이면호 湖南大學校 1995 호남대학교 학술논문집 Vol.16 No.1

Karl Marx, in his Economic and Philosophical Manuscripts, tries to make observations on the essential nature of a man and defines it in terms of work and labor. This idea of his is developed and elaborated more in his later works such as Thesis on Feuerbach, German Ideology and The Capital but, at the same time, these also show some new phases of Marx's thoughts on the definition of a human being. Marx tries to see a man as a total manifestation of all human activities including social relationship as well as labor activity. The main objective of this dissertation is to trace Marx's thoughts on his concept of a man in his earlier works and later ones and find out if there in any dialectical and dialogic relations between the two groups of works. This task requires discussions and analysis of Marx's major ideas, i.e. division of labor, alienation and reification, etc. Finally, as a conclusion, this dissertation attempts to show how Marx's new concept of a man contributed to our understanding of all human beings in the modern age.

동요곡을 중심으로 한 아동음악교육애 관한 고찰

김면세 공주교육대학교 초등연구원 1982 公州敎大論叢 Vol.18 No.-

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한국과학사 자료를 이용한 과학교육의 가능성

이면우 한국초등과학교육학회 2003 초등과학교육 Vol.22 No.2

Science has developed along with human society and history. In today's society ruled by pluralism, and educational approach using the historical materials which represent their own cultures will make science education more effective. The purpose of this study was to search for the meaning of science education related with a history of science, and to suggest the possibility for science education based on Korean history of science. The conclusions of this study is below: (1) The history of science is useful to teaching science in K-12 setting. That is because it was helpful to make a scientific concept and to invite student's interest about learning science. Moreover, it was most suitable to teach the nature of science as well as the relation between science and society. (2) A model which consists of 15 types of science education materials using Korean history was suggested. This model plays a potential role as a R&D framework of developing teaching & learning materials based on the history of Korean Science.

춘천 시내 초등학생의 대기오염과 수질오염에 관한 의사결정 실태와 특징

이면우,長州南海男 춘천교육대학교 과학교육연구소 1998 과학교육연구 Vol.22 No.-

클로로필의 에너지 억제에 대한 용매 특성

朴冕用 건국대학교 1982 學術誌 Vol.26 No.2

The state of aggregation and segregation of chlorophyll-a has been deduced from absorbance and fluorescence spectrophotometry. The aggregated and segregated chl-a were identified by critical point which were appeared on absorbance curves of each λmax. verse the concentration of nucleophilic n-propyl alcohol added into non-polar iso-octane. The fluorescence excitation and emission yields were increased on the increasing of aggregation and decreased on the increasing of segregation.

Silicone-pyridine에 대한 Chlorophyll-a와 -b의 혼합착물의 형광연구(Ⅳ)

박면용,박택규,정구춘 建國大學校基礎科學硏究所 1987 理學論集 Vol.12 No.-

클로필-a와 -b를 혼합물의 상태로 1:2, 1:4, 1:6의 polydimethylethylsilane(0-2 -pyridylethyl methylsilane)에 Mg-pyridine 착물로 디에틸에테르중에서 결합시키고 중합체 사슬을 통한 에너지 이동을 연구하였다. Chl-b에 대한 Chl-a의 첨가량이 증가할수록 Chl-a의 혼합비(5:1, 3:1, 1:1)에 따라 형광수득율이 증가하였다. 반대로 Chl-b가 Chl-a에 비하여 첨가량이 증가할수록 형광수득율이 감소하였다. 최대 형광세기는 Chl-a와 Chl-b에 대하여 결합한 pyridine의 당량농도에서 나타났다. Chl-a에 의하여 흡수된 에너지는 중합체의 사슬을 통하여 Chl-b로 이동하였고 그 이동경향은 dimer>tetramer>hexamer의 순서로 증가하였다. The chlorophyll-a and -b have been bound 1:2, 1:4 and 1:6 polydimethyl ethyl silane(0-2-pyridylehylmethylsilane) as the mixed state to form the complex compound of Mg atom on chlorophyll and pyridine on the polymer in diethyl ether, and studied about the energy migration through the polymer chain in the same solvent. The more chl-a were added to chl-b the more increased fluorescence yields of chl-b were shown it to match for the mixed ratios of chl-a: chl-b in the order of 5:1, 3:1 and 1:1, while chl-a was shown the more decreased fluorescence yields according as the more chl-b were added. The maximum fluorescence intensity were appeared at equivalent pyridine concentration bound to the chl-a and -b. The absorbed energy by chl-a were transfered to chl-b through the chain, and the migration tendencies were on the increase of dimer>tetramer>hexamer.

산화제이철 및 칼슘페라아트 이온 선택성 막전극

박면용,이명재,조동희,원충택 建國大學校基礎科學硏究所 1992 理學論集 Vol.17 No.-

The ion-selective electrode based on ferric oxide and calcium ferric have been studied to ionic sensitivities, selectivities and response behaviors in aqueous solution. The membrane selectrode of ferric oxide was prepared by using α-ferric hydroxide from ferric nitrate solution at pH 4.5∼6.0 . The membrane were sintered at 1,200℃ and 1,350℃. Calcium ferrite was prepared by mixing ferric oxide with calcium oxide on molar ratio of 0.8 : 0.2 and the selectrode membrane based on calcium ferrite was sintered at 1,100℃ Membrane seletrode of ferric oxide was responded without any selectivity to Ag? Ni?, Ca?, Bi?, Ci?, HCO₃?, CIO₄? and NO₃? ion. Membrane seletrode of calcium ferric responded except sensitivity to Ag?, Be?, Cu?, Cr?, Bi?, HCO₃?, CO??, and S??, but their sensitivities were agreed with Nernstain solpe. The selectrode of calcium ferrite was shown reproducible potential response to ions in the solution for six months