公开(公告)号：US20090011991A1

公开(公告)日：2009-01-08

申请号：US12035995

申请日：2008-02-22

申请人： Mamoru Shoji ,  James Synder ,  Dennis Liotta ,  Aiming Sun

发明人： Mamoru Shoji ,  James Synder ,  Dennis Liotta ,  Aiming Sun

IPC分类号： A61K38/36 ,  A61P35/00

CPC分类号： C12Y304/21021 ,  A61K47/6425 ,  C07D213/63 ,  C07D213/64 ,  C12N9/6437

摘要： The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. Conjugates for delivering a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors, and methods of making and using thereof are described herein. The conjugate contains a cytotoxic compound bound to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. The cytotoxic compound is bound to the protein via a linker and a hydrolyzable bond. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage.

摘要翻译： 氟化姜黄素（3,5-双 - （2-氟亚苄基） - 哌啶-4-酮乙酸酯在阻止肿瘤细胞生长方面比顺铂高约十倍。用于递送细胞毒性化合物如姜黄素的缀合物 具体涉及癌细胞和滋养实体瘤的血管内皮细胞，本文描述了制备和使用它们的方法，该缀合物含有与蛋白质结合的细胞毒性化合物，例如对表达蛋白保持高亲和力的因子VIIa 细胞毒性化合物通过接头和可水解键与蛋白质结合，络合时，得到的异源二聚体被内吞，然后通过蛋白水解切割将药物释放到靶细胞内。

公开(公告)号：US09367560B1

公开(公告)日：2016-06-14

申请号：US13326163

申请日：2011-12-14

申请人： David Ely ,  Andrew Coulbeck ,  Trevor Thompson ,  James Synder

发明人： David Ely ,  Andrew Coulbeck ,  Trevor Thompson ,  James Synder

IPC分类号： G06F7/00 ,  G06F17/30

CPC分类号： G06F17/30174 ,  G06F17/30144 ,  G06F17/30575 ,  G06F17/30581

摘要： Disclosed are methods of synchronizing changes in a directory service, comprising receiving a sync request comprising a token from a sync client and returning a response to the sync client comprising a token and changes. Embodiments include collecting and returning changes that are new to the sync client, collecting and returning changes from first and second directory servers, and returning a unified token. The changes may include changes to a dataset that is partitioned over first and second directory servers, and the partitioning may include entry-balancing. Also disclosed are embodiments of a directory service comprising first and second directory servers, each comprising a change set with changes, and a proxy server configured to collect and send changes in the change sets that are new to a sync client, and proxy server and a directory server for use in synchronizing changes in a directory service.

摘要翻译： 公开了一种同步目录服务中的改变的方法，包括从同步客户端接收包括令牌的同步请求，并向包含令牌和更改的同步客户端返回响应。 实施例包括收集并返回对于同步客户端新的改变，收集并返回来自第一和第二目录服务器的改变以及返回统一令牌。 更改可能包括对第一和第二目录服务器上分区的数据集的更改，并且分区可能包括入口平衡。 还公开了包括第一和第二目录服务器的目录服务的实施例，每个目录服务器包括具有改变的改变集合，以及代理服务器，被配置为收集和发送对于同步客户端是新的更改集合的变更，以及代理服务器和 目录服务器用于同步目录服务中的更改。