Object-based storage systems have been widely used for various scenarios such as file storage, block storage, blob (e.g., large videos) storage, etc., where the data is placed among a large number of object storage devices (OSDs). Data placement is critical for the scalability of decentralized object-based storage systems. The state-of-the-art CRUSH placement method is a decentralized algorithm that deterministically places object replicas onto storage devices without relying on a central directory. While enjoying the benefits of decentralization such as high scalability, robustness, and performance, CRUSH-based storage systems suffer from uncontrolled data migration when expanding the capacity of the storage clusters (i.e., adding new OSDs), which is determined by the nature of CRUSH and will cause significant performance degradation when the expansion is nontrivial. This paper presents MapX , a novel extension to CRUSH that uses an extra time-dimension mapping (from object creation times to cluster expansion times) for controlling data migration after cluster expansions. Each expansion is viewed as a new layer of the CRUSH map represented by a virtual node beneath the CRUSH root. MapX controls the mapping from objects onto layers by manipulating the timestamps of the intermediate placement groups (PGs). MapX is applicable to a large variety of object-based storage scenarios where object timestamps can be maintained as higher-level metadata. We have applied MapX to the state-of-the-art Ceph-RBD (RADOS Block Device) to implement a migration-controllable, decentralized object-based block store (called Oasis ). Oasis extends the RBD metadata structure to maintain and retrieve approximate object creation times (for migration control) at the granularity of expansion layers. Experimental results show that the MapX -based Oasis block store outperforms the CRUSH-based Ceph-RBD (which is busy in migrating objects after expansions) by 3.17 × ∼4.31 × in tail latency, and \(76.3\% \) (resp. \(83.8\% \) ) in IOPS for reads (resp. writes).
Antibody-drug conjugates (ADCs) couple tumor cell targeting specificity of monoclonal antibodies with potency of small molecule cytotoxic payloads to overcome the limitations of antibody's moderate cytotoxicity and narrow therapeutic window /poor pharmacokinetics of chemotherapeutic agents[1]. Most of the small molecule drugs used in ADCs now target either microtubules or DNA. Since the highly cytotoxic drugs linked to antibodies may be partially released, which leads to side-effects before they are delivered into the target cancer cells [2], it is important to choose appropriate cytotoxic molecules, linkage structures and conjugation strategies, in order to achieve maximal therapeutic window. To this end, we have designed and synthesized a series of Tubulysin B analogs and then conjugated these articles to anti-Her2 antibodies using different conjugation techniques. Functional assays in vitro based on Her2+ cancer cells showed that some of these novel molecules had significantly lower cytotoxicities as free drugs due to their favorable physiochemical and biological properties, in comparisons with the maytansinoid DM1derivatives, but were more potent than DM1 conjugates in killing the target cells when linked to identical anti-Her2 antibodies. Consistently, in comparisons with T-DM1, our novel ADCs demonstrated improved efficacy as well as reduced systemic side toxicities in Her2-positive xenograft tumor models. The conjugate structures and results from functional assays at both cellular and animal model levels are detailed in the presentation. References: 1. Goldmacher, V.S. and Y.V. Kovtun, Antibody-drug conjugates: using monoclonal antibodies for delivery of cytotoxic payloads to cancer cells. 2011 2(3):. 397-416.. 2. Xie, H., et al., Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. J Pharmacol Exp Ther, 2004. 308(3): 1073-1082. Citation Format: Junxiang Jia, Xiaomai Zhou, Yuanyuan Huang, Hongsheng Xie, Huihui Guo, Shun Gai, Lan Qu, Wenjun Li, Lin Chen, Xing Li, Sanxing Sun, Qingliang Yang, Xiaotao Zhuo, Hangbo Ye, Robert Zhao. Functional evaluation of novel Tubulysin analogs as payloads for antibody-drug conjugates. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4532. doi:10.1158/1538-7445.AM2015-4532
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