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| 1 | MEK inhibition activates STAT signaling to increase breast cancer immunogenicity via MHC-I expression显示文摘Aim:Immunotherapy and immune checkpoint inhibitors(ICI)have changed cancer care for many patients;however,breast cancers have exhibited minimal response to single agent ICI therapy.There is a significant need to identify novel targets capable of increasing cancer cell immunogenicity and response to ICIs in breast cancer.Mitogen activated protein kinase(MAPK)signaling is essential for many cellular processes but the relationship between MAPK signaling and cancer cell immunogenicity is less well understood.Recent reports suggest that MEK inhibition(MEKi)affects the tumor-immune microenvironment by altering the expression of interferon responsive PD-L1 and MHC-I through unknown mechanisms.Methods:Using western blotting and flow cytometry,we sought to determine whether MEKi affects JAK-STAT signaling upstream of PD-L1 and MHC-I expression in a panel of mouse mammary cancer and triple negative breast cancer cell lines.Results:The cell lines tested exhibited increased STAT activation in response to MEKi treatment.Furthermore,MEKi-induced MHC-I and PD-L1 expression are dependent upon STAT1 in MMTV-Neu cells.Interestingly,MEKiinduced STAT activation and interferon-responsive protein expression are abrogated with ErbB-family inhibitor co-treatment in MMTV-Neu cells,suggesting ErbB receptor signaling dependence,but not in basal-like cell lines.Importantly,analysis of basal-like breast cancer patient samples exhibited an inverse relationship between STAT1 and Ras/MAPK activation signatures.Conclusion:These findings suggest that MAPK signaling and STAT activation are inversely related in both mouse and human mammary tumors.This work also supports further study of MEKi to increase STAT signaling and potentially,immunotherapy responses through increased MHC-I and PD-L1 expression. | Derek A.Franklin Jamaal L.James Margaret L.Axelrod Justin M.Balko | 2020 | Cancer Drug Resistance2020，3，3： | 5 |
| 2 | 超声显微镜及其应用显示文摘 | W.S.Gan J.C.Chen L.James C.S.Chong | 1992 | 声学技术1992，11，1： | 2 |
| 3 | Modification of nitrogen remobilization, grain fill and leaf senescence in maize (Zea mays) by transposon insertional mutagenesis in a protease gene显示文摘 | Iain S.Donnison Alan P.Gay HowardThomas Keith J.Edwards DavidEdwards Caron L.James Ann M.Thomas Helen J.Ougham | 2006 | New Phytologist2006，，3： | 1 |
| 4 | 用于宇宙飞船遥测监控和诊断的多任务人工智能系统——SHARP显示文摘宇宙飞船状态良好自动推理原型机(SHARP)是为多任务宇宙飞船和地面数据系统运行能自动进行状态良好判定和状态分析而设计的一个演示系统。SHARP系统演示的最初目标是对旅行者Ⅱ宇宙飞船做远程通讯链路分析,这一演示将在1989年8月当旅行者和与之实时运行平行的海王星交会期间进行。 SHARP系统将传统的计算机科学方法与人工智能技术相结合,以便找出一个检测和分析宇宙飞船及其地面系统潜在问题的有效方法。该系统对宇宙飞船及其它相关的遥测进行实时分析,同时也有能力检查历史性数据。本文扼要地介绍了在喷气推进实验室(JPL)对宇宙飞船和地面系统做监测的过程。它描述了监测旅行者远程通讯子系统所用的现行方法的操作过程,着重介绍与现存技术有关的难点。本文详细说明了在SHARP系统中所采取的克服现行方法局限性的途径,并介绍了SHARP所开发的传统与人工智能两者的解决方法。 | Denise L.Lawson Mark L.James 周双印 | 1992 | 国外导弹与航天运载器1992，，6： | 0 |
| 5 | 用单片ROM改善码同步器的误码性能显示文摘即使滤波器是理想的,采用离散信号处理的前置滤波来抗干扰时,误码性能也要降低。用平均采样器即差分线性滤波器来处理从相关采样获得的统计值时,就会出现误码性能的降低。但是,用正交变换可以减弱已滤波的采样统计的从属性,从而使平均采样表现出近似最优性能。本文为对码同步器的判决产生不利影响的元件提供数学判据和一种替代的正交变换,这种变换通过增加一片 ROM 实现,可以应用于大多数的数字化码同步的设计。 | Calvin L.James 王赞 | 1991 | 遥测遥控1991，0，3： | 0 |
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