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排序方式: 共有1706条查询结果,搜索用时 15 毫秒
1.
Prof. Michael Murray Dr. Ariane Roseblade Dr. Yongjuan Chen Kirsi Bourget Dr. Tristan Rawling 《ChemMedChem》2020,15(2):247-255
Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC50s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion. 相似文献
2.
首次提出了水流泥沙运动水深平均及其力矩方程的概念 ,并从理论上推导出这套方程组。提出水流泥沙运动力矩方程的目的有两个 ,一是在不增加空间维数的情况下可以有效地恢复水流泥沙因子沿水深分布信息 ,克服目前普遍使用的水深平均方程过多地忽略沿水深分布信息的缺点 ;二是增强模型的模拟能力。针对这两个目的是否能真正得到体现 ,分别从理论和实验室资料两个方面对新推导的力矩方程进行了全面的检验。理论验证结果表明 ,一维的力矩方程除了能模拟水深平均的流速和含沙量 ,还能够较好地模拟水流泥沙因子沿水深分布信息 ,这充分说明了一维力矩方程的二维特性。为了检验力矩方程的模拟能力 ,特别选取了一些极端的水流泥沙运动实验 ,如清水冲刷、点源加沙和深槽回淤等。模拟结果表明 ,力矩方程对于这些极端的水沙运动具有较好的模拟能力 相似文献
3.
如何利用现有的数字CATV系统开展各种增值业务已成为一个重要课题.首先简要介绍了数字CATV和超宽带技术,然后给出了两种超宽带技术在现有数字CATV系统中的应用方案,利用这些方案可以有效地开展各项增值业务. 相似文献
4.
5.
本文介绍了公用和专用分组交换数据网的现状后,说明了开展标准的增值业务系统的重要性。论述了典型的增值业务系统-电子邮件和传真存储转发系统。 相似文献
6.
溢流反弧段水流边界层有关概念的探讨 总被引:1,自引:1,他引:0
本文对溢流反孤段水流边界层的定义方法进行分析讨论。在分析及弧段流速分布的基础上提出离心力附加边界层厚度和粗糙度附加边界层厚度的概念,研究了壁面曲率和壁面粗糙度对溢流反弧段边界层发展的影响。 相似文献
7.
从流行病学、临床症状、病理变化和实验室检验四个方面对鸡传染性喉气管炎进行了诊断,并做了药物治疗对比试验.结果表明,杀病毒药(消毒王)加清热解毒、止咳平喘中草药配合治疗鸡传染性喉气管炎,效果更好,能较快地制止病鸡死亡,显著降低死亡率及减少药物治疗费用. 相似文献
8.
Artificial added mass instabilities in sequential staggered coupling of nonlinear structures and incompressible viscous flows 总被引:1,自引:0,他引:1
Christiane Förster Wolfgang A. Wall 《Computer Methods in Applied Mechanics and Engineering》2007,196(7):1278-1293
Within this paper the so-called artificial added mass effect is investigated which is responsible for devastating instabilities within sequentially staggered Fluid-structure Interaction (FSI) simulations where incompressible fluids are considered.A discrete representation of the added mass operator MA is given and ‘instability conditions’ are evaluated for different temporal discretisation schemes. It is proven that for every sequentially staggered scheme and given spatial discretisation of a problem, a mass ratio between fluid and structural mass density can be found at which the coupled system becomes unstable. The analysis is quite general and does not depend upon the particular spatial discretisation schemes used. However here special attention is given to stabilised finite elements employed on the fluid partition. Numerical investigations further highlight the results. 相似文献
9.
Benjamin Caulier Jorrit M. Enserink Sbastien Wlchli 《International journal of molecular sciences》2021,22(9)
Chimeric antigen receptor (CAR) therapy is a promising modality for the treatment of advanced cancers that are otherwise incurable. During the last decade, different centers worldwide have tested the anti-CD19 CAR T cells and shown clinical benefits in the treatment of B cell tumors. However, despite these encouraging results, CAR treatment has also been found to lead to serious side effects and capricious response profiles in patients. In addition, the CD19 CAR success has been difficult to reproduce for other types of malignancy. The appearance of resistant tumor variants, the lack of antigen specificity, and the occurrence of severe adverse effects due to over-stimulation of the therapeutic cells have been identified as the major impediments. This has motivated a growing interest in developing strategies to overcome these hurdles through CAR control. Among them, the combination of small molecules and approved drugs with CAR T cells has been investigated. These have been exploited to induce a synergistic anti-cancer effect but also to control the presence of the CAR T cells or tune the therapeutic activity. In the present review, we discuss opportunistic and rational approaches involving drugs featuring anti-cancer efficacy and CAR-adjustable effect. 相似文献
10.
Jaewan Jeon Sungmin Lee Hyunwoo Kim Hyunkoo Kang HyeSook Youn Sunmi Jo BuHyun Youn Hae Yu Kim 《International journal of molecular sciences》2021,22(10)
Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs. 相似文献