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    • 51. 发明申请
    • PROTEIN AGENT FOR DIABETES TREATMENT AND BETA CELL IMAGING
    • 用于糖尿病治疗和细胞成像的蛋白剂
    • WO2011050052A2
    • 2011-04-28
    • PCT/US2010/053361
    • 2010-10-20
    • GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.LIU, Zhi-RenYANG, JieXU, BingZHOU, WangdaXUE, Shengui
    • LIU, Zhi-RenYANG, JieXU, BingZHOU, WangdaXUE, Shengui
    • C07K19/00A61K38/26A61K49/14G01N33/52A61P3/10
    • A61K38/26A61K38/00A61K47/60A61K49/085C07K14/605C07K2319/00
    • Glucagon-like peptide-1 (GLP-1 ) is a member of a large family of incretin hormones secreted in nutrient-dependent response. GLP-1 acts on GLP-1 receptor (GLP-1 R) that is highly expressed on pancreatic β-cells. The peptide has great potential for development of diabetes treatment and diagnosis. However, the pharmaceutical effects of the peptide suffer from in vivo instability and short life due to degradation by Dipeptidylpeptidase-1 (DPP-4). The 30 amino acid peptide GLP-1 has been integrated into a stable host protein human calbindin D9k. The fusion protein binds to GLP-1 R as demonstrated by immunostaining analyses of GLP-1 R expressing cells. The fusion protein agents can be useful for both diabetes treatment and GLP-1 R receptor targeting MR imaging. The fusion protein has a size about 14 kDa, which enables efficient tissue penetration and retention, and an extended circulation time, is stable, remaining intact and retaining activity after 48 hours incubation with 75% human serum. The protein retains its native folded structure after boiling for ten minutes forming the basis of an experimental protocol for large scale production of the fusion protein (>30 mg/l bacterial culture). No toxicity has been observed with tests on mice. One aspect of the disclosure, therefore, provides a fusion protein comprising a first peptide characterized by selectively binding to a site of a target cell and linked to a second peptide, where the fusion protein is more stable than the first peptide alone. In embodiments of this aspect of the disclosure, the fusion protein may further comprise a detectable label attached thereto. In some embodiments of this aspect of the disclosure, the first peptide of the fusion protein may be glucagon-like peptide-1 (GLP-1 ), glucagon-like peptide-1 (GLP-1 )(7-36), or glucagon-like peptide-1 (GLP-1 ) (9-36), or a conservative variant thereof.
    • 胰高血糖素样肽-1(GLP-1)是营养依赖性反应中分泌的大肠激素的成员之一。 GLP-1作用于在胰腺β细胞上高表达的GLP-1受体(GLP-1R)。 该肽具有发展糖尿病治疗和诊断的巨大潜力。 然而,由于二肽基肽酶-1(DPP-4)的降解,肽的药物作用遭受体内不稳定性和短寿命。 30个氨基酸的肽GLP-1已经被整合到稳定的宿主蛋白人类calbindin D9k中。 如通过GLP-1R表达细胞的免疫染色分析所证明的,融合蛋白与GLP-1R结合。 融合蛋白剂可用于糖尿病治疗和靶向MR-1的受体受体。 融合蛋白具有约14kDa的大小,其能够有效的组织穿透和保留,并且延长的循环时间是稳定的,在75%人血清孵育48小时后保持完整和保留活性。 蛋白质在煮沸10分钟后保持其天然折叠结构,形成大规模生产融合蛋白(> 30mg / l细菌培养物)的实验方案的基础。 在小鼠试验中没有观察到毒性。 因此,本公开的一个方面提供了包含第一肽的融合蛋白,其特征在于选择性结合靶细胞的位点并连接到第二个肽,其中融合蛋白比单独的第一个肽更稳定。 在本公开的该方面的实施方案中,融合蛋白还可包含附着于其上的可检测标记。 在本公开的该方面的一些实施方案中,融合蛋白的第一肽可以是胰高血糖素样肽-1(GLP-1),胰高血糖素样肽-1(GLP-1)(7-36)或胰高血糖素 样肽-1(GLP-1)(9-36)或其保守变体。
    • 52. 发明申请
    • SYSTEMS AND METHODS FOR DRYING A ROTATING SUBSTRATE
    • WO2007084952A3
    • 2007-07-26
    • PCT/US2007/060709
    • 2007-01-18
    • AKRION TECHNOLOGIES, INC.LIU, Zhi, LewisKASHKOUSH, IsmailLEE, Hanjoo
    • LIU, Zhi, LewisKASHKOUSH, IsmailLEE, Hanjoo
    • F26B11/00
    • A method of drying a surface of a substrate is provided. The method includes supporting and rotating a substrate; applying a liquid to the substrate surface at or near a rotational center point via a liquid dispenser (so that a film of the liquid is formed on the surface); applying a drying fluid to she substrate surface at a predetermined distance from the rotational center point via one or more drying fluid dispensers; and manipulating the drying fluid dispenser(s) so that the location at which the drying fluid is applied to the substrate is moved in a direction toward the rotational center point, while at the same time manipulating the liquid dispenser so that the location at which the liquid is applied to the substrate is moved in a direction outward from the rotational center point. The liquid dispenser and drying fluid dispensers) noted above can be located on and/or within an assembly. The assembly can include a first dispenser, a second dispenser, and a third dispenser. The first dispenser supplies liquid while the second and third dispensers supply drying fluid, where the second dispenser has a larger opening than the third dispenser. The second and third dispensers are positioned on the assembly next to one another and spaced from the first dispenser. Further, the second dispenser is located between the third dispenser and the first dispenser, such that the first dispenser is capable of linearly leading the second and third dispensers during movement.