During the past three decades,studies have shown that tumor cells could"manipulate"host immunity to escape the immune defenses in the tumor microenvironment.One of the most important underlying mechanisms is...During the past three decades,studies have shown that tumor cells could"manipulate"host immunity to escape the immune defenses in the tumor microenvironment.One of the most important underlying mechanisms is immune-suppression regulated by programmed cell death-1 or its ligand 1(PD-1/PD-L1),which makes PD-1/PD-L1 blockadea promising target of cancer immune-therapy.Tumors could suppress immuno-response of T cells by activating PD-1/PD-L1 signaling pathway.Therefore,inhibiting the interaction between PD-1 and PD-L1 could reconstitute the enduring antitumor immunity in the tumor microenvironment via enhancing the T-cell response,there after augmenting the endogenous antitumor force of the immune system.Along these lines,inhibitors of PD-1/PD-L1 has been applied in multiple clinical trials against various types of tumors.Recent studies indicated that PD-1/PD-L1 blockade have demonstrated high efficacy and safety against melanoma,lung,kidney and several other solid tumors,as well as hematological malignancies.Nevertheless,the efficacy of this checkpoint blockade approach is not universal.Some investigation suggested that lack of responses to anti-PD-1/PD-L1 therapy of patients without PD-1/PD-L1 over-expression was expected.In this review,we summarize the history and current understanding of multiple intrinsic and extrinsic mechanisms via which PD-1/PD-L1 is regulated and research advances in preclinical/clinical aspects of PD-1/PD-L1,as well as significance and perspectives regarding the PD-1/PD-L1 blockade in immune-antitumor therapy.展开更多
A scheduling scheme is proposed to reduce execution time by means of both checkpoint sharing and task duplication under a peer-to-peer(P2P) architecture. In the scheme, the checkpoint executed by each peer(i.e., a res...A scheduling scheme is proposed to reduce execution time by means of both checkpoint sharing and task duplication under a peer-to-peer(P2P) architecture. In the scheme, the checkpoint executed by each peer(i.e., a resource) is used as an intermediate result and executed in other peers via its duplication and transmission. As the checkpoint is close to a final result, the reduction of execution time for each task becomes higher, leading to reducing turnaround time. To evaluate the performance of our scheduling scheme in terms of transmission cost and execution time, an analytical model with an embedded Markov chain is presented. We also conduct simulations with a failure rate of tasks and compare the performance of our scheduling scheme with that of the existing scheme based on client-server architecture. Performance results show that our scheduling scheme is superior to the existing scheme with respect to the reduction of execution time and turnaround time.展开更多
互联网安全解决方案供应商Check Point软件技术有限公司宣布，“支持专业人员协会”（The Association of Support Professionals，ASP）连续3年评选Check Point为年度十大最佳Web支持站点之一，以表彰其网上服务与支持的卓越表现。Chec...互联网安全解决方案供应商Check Point软件技术有限公司宣布，“支持专业人员协会”（The Association of Support Professionals，ASP）连续3年评选Check Point为年度十大最佳Web支持站点之一，以表彰其网上服务与支持的卓越表现。Check Point公司网站中的Check Point支持中心网页为用户提供丰富的知识资源、用户论坛、实时交流（Live Chat）及远程访问功能，不断提升客户满意度。展开更多
文摘During the past three decades,studies have shown that tumor cells could"manipulate"host immunity to escape the immune defenses in the tumor microenvironment.One of the most important underlying mechanisms is immune-suppression regulated by programmed cell death-1 or its ligand 1(PD-1/PD-L1),which makes PD-1/PD-L1 blockadea promising target of cancer immune-therapy.Tumors could suppress immuno-response of T cells by activating PD-1/PD-L1 signaling pathway.Therefore,inhibiting the interaction between PD-1 and PD-L1 could reconstitute the enduring antitumor immunity in the tumor microenvironment via enhancing the T-cell response,there after augmenting the endogenous antitumor force of the immune system.Along these lines,inhibitors of PD-1/PD-L1 has been applied in multiple clinical trials against various types of tumors.Recent studies indicated that PD-1/PD-L1 blockade have demonstrated high efficacy and safety against melanoma,lung,kidney and several other solid tumors,as well as hematological malignancies.Nevertheless,the efficacy of this checkpoint blockade approach is not universal.Some investigation suggested that lack of responses to anti-PD-1/PD-L1 therapy of patients without PD-1/PD-L1 over-expression was expected.In this review,we summarize the history and current understanding of multiple intrinsic and extrinsic mechanisms via which PD-1/PD-L1 is regulated and research advances in preclinical/clinical aspects of PD-1/PD-L1,as well as significance and perspectives regarding the PD-1/PD-L1 blockade in immune-antitumor therapy.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2012R1A1A4A0105777)supported by the MSIP (Ministry of Science, ICT and Future Planning), Korea, under the ITRC (Information Technology Research Center) support program (NIPA-2013-H030113-4007) supervised by the NIPA (National IT Industry Promotion Agency)
文摘A scheduling scheme is proposed to reduce execution time by means of both checkpoint sharing and task duplication under a peer-to-peer(P2P) architecture. In the scheme, the checkpoint executed by each peer(i.e., a resource) is used as an intermediate result and executed in other peers via its duplication and transmission. As the checkpoint is close to a final result, the reduction of execution time for each task becomes higher, leading to reducing turnaround time. To evaluate the performance of our scheduling scheme in terms of transmission cost and execution time, an analytical model with an embedded Markov chain is presented. We also conduct simulations with a failure rate of tasks and compare the performance of our scheduling scheme with that of the existing scheme based on client-server architecture. Performance results show that our scheduling scheme is superior to the existing scheme with respect to the reduction of execution time and turnaround time.
文摘互联网安全解决方案供应商Check Point软件技术有限公司宣布，“支持专业人员协会”（The Association of Support Professionals，ASP）连续3年评选Check Point为年度十大最佳Web支持站点之一，以表彰其网上服务与支持的卓越表现。Check Point公司网站中的Check Point支持中心网页为用户提供丰富的知识资源、用户论坛、实时交流（Live Chat）及远程访问功能，不断提升客户满意度。
