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通过抑制 P 糖蛋白介导的药物耐受持久细胞中有毒脂质过氧化副产物的清除，有效靶向治疗乳腺癌
Therapy resistance has long been considered to occur through the selection of pre-existing clones equipped to survive and quickly regrow, or through the acquisition of mutations during chemotherapy. Here we show that following in vitro treatment by chemotherapy, epithelial breast cancer cells adopt a transient drug tolerant phenotype characterized by cell cycle arrest, epithelial-to-mesenchymal transition (EMT) and the reversible upregulation of the multidrug resistance (MDR) efflux transporter P-glycoprotein (P-gp). The drug tolerant persister (DTP) state is reversible, as cells eventually resume proliferation, giving rise to a cell population resembling the initial, drug-naïve cell lines. However, recovery after doxorubicin treatment is almost completely eliminated when DTP cells are cultured in the presence of the P-gp inhibitor Tariquidar. Mechanistically, P-gp contributes to the survival of DTP cells by removing reactive oxygen species-induced lipid peroxidation products resulting from doxorubicin exposure. In vivo, prolonged administration of Tariquidar during doxorubicin treatment holidays resulted in a significant increase of the overall survival of Brca1 − / − ;p53 − / − mammary tumor bearing mice. These results indicate that prolonged administration of a P-gp inhibitor during drug holidays would likely benefit patients without the risk of aggravated side effects related to the concomitantly adminis tered toxic chemotherapy. Effective targeting of DTPs through the inhibition of P-glycoprotein may result in a paradigm shift, changing the focus from countering drug resistance mechanisms to preventing or delaying therapy resistance.
在堆肥中添加EM4激活剂和有机渗滤液水的添加棕榈油Husnawati Yahya *，Alfis Yusri
棕榈油加工产生的空水果束废物，具有较高的有机含量。空的水果束每年产生多达600万吨废物，而这种废物尚未被广泛使用，因此可以成为未来污染等环境问题。使用废物的替代方法是将它们转化为有机肥料或堆肥。因此，本研究旨在通过使用渗滤液激活剂来分析和比较EM4激活剂堆肥的结果，每个激活剂的堆肥时间以及堆肥质量的效果以及SNI的质量指的是SNI 19-7030-2004。在这项研究中，通过添加1升EM4激活剂并增加1升浸出水，进行了三个无需治疗的实验，进行了21天的堆肥过程。测得的参数是物理，温度，湿度，pH，C，N，P，K和C/N-RATIO。The results of this study indicate that composting with EM4 activator resulting composting pH level of 4.4 - 6.2, humidity of 1.5 - 70%, temperature of 29-38 °C, brownish black in colour, rough and hard in textures and soil-like (earthy) smell while composting using leachate water has a pH of 4.6 - 6.5, humidity of 3.9 - 80%, temperature of 29- 38 °C and brownish black in颜色，粗糙的质地和略微臭。带有EM4激活剂的堆肥比使用渗滤液更快。在质量方面，使用EM4激活剂的堆肥产生了更高质量的堆肥，与渗滤液活化剂堆肥相比，堆肥质量接近SNI 19-730-2004要求。关键字：堆肥，空束，激活剂，EM4，渗滤液。。
1956 年公司法，其 ltegistem.l 办公室位于地块编号...
合并后公司，合并后公司的自备发电能力将提高至 98 兆瓦，从而提供急需的额外 25 兆瓦电力容量，以满足合并后公司电力需求的短缺，以具有竞争力的成本确保向其炼钢单位不间断供电，从而提高其炼钢厂的产能利用率，并通过经营杠杆节省成本。值得一提的是，合并后公司的工厂所在地不允许增加新的燃煤发电能力
经济复苏和复原计划
• 对送货服务的需求增加 • 导致对司机的需求增加 • 随着送货变得越来越重要，强调道路维护的重要性 • 更加关注公共卫生 • 企业“上游”供应商的供应短缺 • 导致供应中断、特定产品短缺以及有时价格上涨。 • 先前存在的卡车短缺问题恶化（包括回程短缺和缺乏满载需求） • 导致创建出口业务的需求增加 • 导致对司机的需求增加 • 对住房的需求增加 • 导致新居民对宽带和手机服务的需求增加 • 导致建筑材料成本增加和建筑行业劳动力持续短缺 • 导致租金和售价上涨，以及经济适用房短缺加剧 • 非农私营企业就业总额急剧下降，休闲和酒店业损失最为严重。佛蒙特州劳工部经季节性调整后的就业数据显示，许多行业正在恢复就业，但休闲和酒店业的就业复苏速度最慢。1 • 劳动力供应短缺正在影响许多小企业维持或发展业务的能力。• 由于托儿所和学校关闭，女性退出劳动力市场
亲爱的 Fathima M
• 开发了一种由蛋壳制成的补充剂，并在国际会议上获得了最佳论文演讲奖，从而使人们对替代钙源的认识提高了 15%。 • 开展饮食咨询课程，使患者的营养状况在三个月内平均改善了 10%。 • 在高血压案例研究中调查了生活方式改变对血压控制的有效性，从而开发了一种饮食干预措施，使平均血压水平降低了 12%。 • 促进糖尿病检查计划，使 50 人早期发现糖尿病并随后参加管理计划。 • 领导了一个创新细胞项目，专注于开发健康的披萨品种，使校园餐饮设施中营养披萨的销量增加了 20%。 • 组织并执行了以小米为基础的活动“食品中心 2023”，使当地社区消费者对小米产品的认识和消费量增加了 30%。
人寿/意外伤害及伤残保险和短期伤残保险计划 - Trustmark
AD&D 除外责任 以下情况不予赔付：故意自残，无论神志清醒与否 • 自杀或企图自杀，无论神志清醒与否 • 因犯下或企图犯下重罪而造成的损失 • 因从事非法职业而造成的损失 • 因乘坐任何类型的飞机而造成的伤害，但作为商用飞机的付费乘客除外 • 战争或战争行为，无论是否宣布 • 身体或精神疾病 • 任何类型的疝气 • 细菌感染及其医疗或外科治疗 • 因意外摄入有毒食物而导致的感染 • 医疗或外科治疗，但因承保伤害而导致并在受保伤害发生后 90 天内进行的手术除外
mnsure-Enrollment-Coortinator-Job-Description。 ...
Client intake and triage resulting in a high quality client record and effective assignment of client appointments to maximize Navigator capacity and specialty knowledge Appointment pre-screening, MNsure identify proofing and where necessary initiate MNsure manual account creation to promote client service and appointment efficiency Client issue resolution for situations that do not require a MNsure application or a full appointment slot including verifying whether coverage is active,与健康计划或服务机构联系以请求会员卡，报告地址更改，要求为家庭成员（孕妇，新生儿等）提供新的保险。执行指定的其他职责), resolving incomplete applications, sending verifications to servicing agencies on behalf of clients, and reading and understanding notices Incoming client document management involving confidential handling of client data and documentation, use of supporting technology, associated case noting and forwarding verifications to servicing agencies Assist MNsure Navigators to resolve pending cases including coordination with client, Navigators and administering agencies as well as management of required client documentation Promptly answer, record, and complete all client requests, phone calls, questions, or concerns using ECM or other designated systems Protect client confidential data and documentation Complete annual MNsure certification to become a certified MNsure Navigator Responsible for staying current on MNsure policies, Affordable Care Act (ACA) rules, upcoming changes, and effect the political process has on the current programs Gain understanding of the culture以及所服务的客户的价值观，表现出对来自不同背景的客户的尊重和敏感性告知客户可用的社区资源，并向内部和外部专家推荐。
