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    • 1. 发明授权
    • Apparatus for producing ions of thermally labile or nonvolatile solids
    • 用于产生热不稳定或非挥发性固体的离子的装置
    • US4175234A
    • 1979-11-20
    • US916151
    • 1978-06-16
    • Donald F. HuntJeffrey Shabanowitz
    • Donald F. HuntJeffrey Shabanowitz
    • H01J49/14H01J49/16H01J27/00
    • H01J49/145H01J49/16
    • An apparatus for ionizing and vaporizing non-volatile or thermally labile molecules of a sample for introduction into a mass spectrometer analyzer which comprises a housing containing an ionization chamber; an ion exit port for the introduction of gaseous ions from said ionization chamber into a mass spectrometer analyzer on the portion of the housing attached to said mass spectrometer analyzer; inlet means for introducing a gaseous reactant into said ionization chamber within said housing; inlet means for admitting high energy radiation into said ionization chamber within said housing to at least partially ionize the molecules of said gaseous reactant; aperture means open into said ionization chamber of said housing for admitting a conductive emitter characterized by having a conductive element of a highly irregular surface upon which is deposited said sample for analysis into said mass spectrometer analyzer; and a vacuum exit aperture in said housing by which the pressure within said ionization chamber can be reduced.
    • 一种用于离子化和蒸发样品的非挥发性或热不稳定分子的装置,用于引入质谱仪分析仪,其包括含有电离室的壳体; 离子出口,用于将气态离子从所述电离室引入质谱仪分析仪,所述质谱仪分析仪附着在所述质谱仪分析仪上​​; 用于将气体反应物引入所述壳体内的所述电离室的入口装置; 入口装置,用于将高能量辐射进入所述壳体内的所述电离室,以使所述气态反应物的分子至少部分电离; 开口意味着通向所述壳体的所述电离室,用​​于允许导电发射器,其特征在于具有高度不规则表面的导电元件,在其上沉积所述样品用于分析所述质谱仪分析仪; 以及所述壳体中的真空出口孔,通过该真空出口孔可以减小所述电离室内的压力。
    • 9. 发明授权
    • Antigens targeted by prevalent pathogennic T cells in type 1 diabetes and uses thereof
    • 1型糖尿病中流行的病原性T细胞靶向的抗原及其用途
    • US08758767B2
    • 2014-06-24
    • US10557273
    • 2004-05-20
    • Teresa P. DiLorenzoAnne M. EvansDonald F. HuntScott M. LiebermanStanley G. NathensonPere SantamariaJeffrey Shabanowitz
    • Teresa P. DiLorenzoAnne M. EvansDonald F. HuntScott M. LiebermanStanley G. NathensonPere SantamariaJeffrey Shabanowitz
    • A61K39/00A61K39/385
    • C07K14/4711
    • The present invention is based on the identification of a predominant ligand of CD8+ T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8+ T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8+ T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN(A/I/L/V)FL (SEQ ID NO:3), FLWSVFWLI (SEQ ID NO:4), (T/A)YY(G/T)FLNFM (SEQ ID NO:5), LR(L/V)(F/L)(G/N)IDLL (SEQ ID NO:6), KWCANPDWI (SEQ ID NO:7), and SFCKSASIP (SEQ ID NO:8). Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8+ T cell that is cytotoxic to pancreatic islet β-cells from destroying a mammalian β-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.
    • 本发明基于负责1型糖尿病的CD8 + T细胞的主要配体的鉴定。 该配体是胰岛特异性葡萄糖-6-磷酸酶催化亚单位相关蛋白(IGRP)。 鉴定了来自IGRP的几种CD8 + T细胞结合肽,包括含有IGRP序列的氨基酸206-214的肽,其对自身免疫性糖尿病中病原性CD8 + T细胞最流行的T细胞受体具有高亲合力。 因此,本发明提供包含YLKTN(A / I / L / V)FL(SEQ ID NO:3),FLWSVFWLI(SEQ ID NO:4),(T / A)YY(G / T)FLNFM SEQ ID NO:5),LR(L / V)(F / L)(G / N)IDLL(SEQ ID NO:6),KWCANPDWI(SEQ ID NO:7)和SFCKSASIP(SEQ ID NO:8) 。 还提供了长度为8-10个氨基酸且与哺乳动物IGRP完全同源的寡肽组合物,其中寡肽能够结合人MHC I类分子。 此外,提供使用上述组合物治疗哺乳动物的各种方法,其中哺乳动物处于或具有1型糖尿病的风险。 还提供了防止对胰岛细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物和细胞的方法,其中所述方法也使用上述组合物。 还提供了用于确定哺乳动物是否处于或患有1型糖尿病的风险的方法,其中所述方法使用上述组合物。
    • 10. 发明申请
    • Antigens Targeted by Prevalent Pathogennic T Cells in Type 1 Diabetes and Uses Thereof
    • 1型糖尿病中普遍的病原性T细胞靶向的抗原及其用途
    • US20080153112A1
    • 2008-06-26
    • US10557273
    • 2004-05-20
    • Teresa P. DiLorenzoAnne M. EvansDonald F. HuntScott M. LiebermanStanley G. NathensonPere SantamariaJeffrey Shabanowitz
    • Teresa P. DiLorenzoAnne M. EvansDonald F. HuntScott M. LiebermanStanley G. NathensonPere SantamariaJeffrey Shabanowitz
    • A61K31/711A61K38/08A61P3/10C07H21/02C07H21/04C07K14/00C07K7/00C12N5/06G01N33/567
    • C07K14/4711
    • The present invention is based on the identification of a predominant ligand of CD8+ T cells that are responsible eq for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8+ T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8+ T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN/A/I/L/V)FL, FLWSVFWLI, (T/A)YY/G/T)FLNFM, LR(LV)(F/L)(G/N)IDLL, KWCANPDWI, and SFCKSASIP. Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8+ T cell that is cytotoxic to pancreatic islet β-cells from destroying a mammalian β-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.
    • 本发明基于鉴定负责1型糖尿病的CD8 + T细胞的主要配体。 该配体是胰岛特异性葡萄糖-6-磷酸酶催化亚单位相关蛋白(IGRP)。 鉴定了来自IGRP的几种CD8 + T细胞结合肽,包括含有IGRP序列的氨基酸206-214的肽,其对自身免疫性糖尿病中病原性CD8 + T细胞最流行的T细胞受体具有高亲合力。 本发明提供包含YLKTN / A / I / L / V)FL,FLWSVFWLI,(T / A)YY / G / T)FLNFM,LR(LV)(F / L)(G / N)的寡肽和多肽组合物 IDLL,KWCANPDWI和SFCKSASIP。 还提供了长度为8-10个氨基酸且与哺乳动物IGRP完全同源的寡肽组合物,其中寡肽能够结合人MHC I类分子。 此外,提供使用上述组合物治疗哺乳动物的各种方法,其中哺乳动物处于或具有1型糖尿病的风险。 还提供了防止对胰岛β细胞具有细胞毒性的CD8 + T细胞破坏哺乳动物β细胞的方法,其中该方法也使用上述组合物。 还提供了用于确定哺乳动物是否处于或患有1型糖尿病的风险的方法,其中所述方法使用上述组合物。