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摘要： Purpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages, and mast cells, we identified the relevance of nonimmune cell types for breast cancer survival and therapy benefit, including fibroblasts, myoepithelial cells, muscle cells, endothelial cells, and seven distinct epithelial cell types. Experimental Design: Using single-cell sequencing data, we generated reference profiles for all these cell types. We used these reference profiles in deconvolution algorithms to optimally detangle the cellular composition of more than 3,500 primary breast tumors of patients that were enrolled in the SCAN-B and MATADOR clinical trials, and for which bulk mRNA sequencing data were available. Results: This large data set enables us to identify and subsequently validate the cellular composition of miaoenvironments that distinguish differential survival and treatment benefit for different treatment regimens in patients with primary breast cancer. In addition to immune cells, we have identified that survival and therapy benefit are characterized by various contributions of distinct epithelial cell types. Conclusions: From our study, we conclude that differential survival and therapy benefit of patients with breast cancer are characterized by distinct microenvironments that include specific populations of immune and epithelial cells.

关键词： 存在性   唯一性   分数阶微分方程   Arzelà-Ascoli定理  

摘要： 文章研究了具有两个阻尼项分数阶微分方程的动力系统解的存在性和唯一性.该文考虑以下具有两个阻尼项的分数阶微分方程{^(c)D^(α)_(0+)x(t)-A^(c)D^(β)_(0+)x(t)-B^(c)D^(γ)_(0+)x(t)=f(t,x(t)),t∈J:=[0,T],x(0)=x_(0),x′(0)=x′_(0),x″(0)=x″_(0),其中0<γ≤1<β≤2<α≤3,0

关键词： 高考复习   导数压轴题   对数函数   函数不等式   指数函数   出奇制胜   主要考点   事半功倍  

摘要： 指数函数和对数函数是高考复习中的重点和难点,也是导数压轴题的主要考点.函数不等式ex≥x+1和lnx≤x-1是两个基本的指对函数不等式,在解答导数压轴题时如果能充分运用这两个不等式,往往使一些难题迎刃而解,甚至收到出奇制胜,事半功倍的效果.本文举例说明这些指对函数不等式在导数压轴题中的应用.

关键词： 多缸液压机   模糊自整定积分分离PID控制   相邻交叉耦合   同步控制   同步误差  

摘要： 为了减小多缸液压机对给定位移的跟踪误差和液压缸之间的同步误差,设计了相邻交叉耦合模糊自整定积分分离PID同步控制器。以液压阀的阀控电压为控制量,以活塞杆位移为输出量,建立了同步控制系统的动力学方程。选择相邻交叉耦合同步控制方案作为基础方案,将积分分离PID控制与模糊理论相结合,提出了模糊自整定积分分离PID控制方法。仿真结果表明:从超调量、调节时间、同步误差的角度讲,相邻交叉耦合同步控制的效果优于主从同步方案和同等同步方案,模糊自整定积分分离PID控制优于模糊PID控制。经3000 kN液压机控制实验验证,在最大负载为270.4 kN的情况下,液压机压制过程的超调量为3.2%,最大同步误差为0.17 mm,说明设计的控制器具有较好的同步控制效果。

关键词： 高中数学解题   导数教学   数学解题  

摘要： 随着社会发展速度逐步提升,知识更新换代的速率也上升到了一个全新的高度.为确保知识的更新化,及时掌握先进知识,在进行学科学习时应当树立学无止境的观念,数学作为一门专业性较强的学科更应该做到这样.兴趣能够促进数学学习者主动学习数学知识,但学生在学习层面仅具有兴趣是完全不够的,同时还需要教师的指导,以这种方式进行学习,学生在数学学习当中才能做到独立化、个性化和全面发展.基于此,以下对导数在高中数学解题中的应用进行了探讨,以供参考.

关键词： 风景/地形   微分   集团的临时性  

摘要： 不同于众多西部片里的“大西部”,出身于黑色电影的安索尼·曼导演的西部片呈现了某种趋向于“小”的面貌。在空间景观呈现上,“风景-人物镜头”取代了单纯的风景空镜头,在动作高潮段落里,人物视线、运动受到限制的山岩绝壁取代了一马平川的荒原。这里有他突出“地形”特征的“小西部”。这种“小”全方位渗透在诸多元素中:枪战时的狭窄视线,发现陌生者时的镜头剪辑点的选择,知觉和行动的同时发生,在信任和背叛之间摇摆不定的西部人“团伙”的临时性,无以区分是假戏还是真情的“罗曼”之夜……本文切入作品细部对上述事项逐一讨论,兼顾戈达尔提及的安索尼·曼西部片中的“植物性”和“矿物性”,尝试描画出一种以“小”为特征的生的经验。

关键词： 综合考查   压轴题   恒成立   函数单调性   最值   深度与广度   参数范围问题   导数  

摘要： 导数是研究函数单调性、极值(或最值)的有力工具,而且一直是历年高考的热点和难点。高考对导数的考查力度、难度、深度与广度都在不断变化,常将导数与不等式有机结合,并作为压轴题进行综合考查。下面对“由含参数的不等式恒成立求参数范围问题”的解法进行归类,希望对同学们有所帮助。

关键词： 非自治刚性随机微分方程   正则Euler-Maruyama分裂方法   收敛性   稳定性  

摘要： 本文研究了数值求解非自治随机微分方程的正则Euler-Maruyama分裂(CEMS)方法,该方程的漂移项系数带有刚性且允许超线性增长,扩散项系数满足全局Lipschitz条件.首先,证明了CEMS方法的强收敛性及收敛速度.其次,证明了在适当条件下CEMS方法是均方稳定的.进一步,利用离散半鞅收敛定理,研究了CEMS方法的几乎必然指数稳定性.结果表明,CEMS方法在漂移系数的刚性部分满足单边Lipschitz条件下可保持几乎必然指数稳定性.最后通过数值实验,检验了CEMS方法的有效性并证实了我们的理论结果.

摘要： Noise trauma involves a plethora of mechanisms including reactive oxygen species, apoptosis, tissue damage, and inflammation. Recently, circadian mechanisms were also found to contribute to the vulnerability to noise trauma in mice, with greater damage occurring during their active phase (nighttime), when compared to similar noise exposures during their inactive phase (daytime). These effects seem to be regulated by mechanisms involving Bdnf responses to noise trauma and circulating levels of corticosterone (CORT). However, recent studies using different noise paradigms show contradicting results and it remains unclear how universal these findings are. Here we show that these findings differ even between substrains of mice and are restricted to a narrow window of noise intensity. We found that CBA/Sca mice exposed to 103 dB SPL display differential day/night noise sensitivity as measured by auditory brain stem responses (ABRs), but not at 100 (where full recovery is observed in day or night exposed mice) or 105 dB SPL (where permanent damage is found in both groups). In contrast, neither CBA/CaJ or CBA/JRj displayed such differences in day/night noise sensitivity, whatever noise intensity used. These effects appeared to be independent from outer hair cell function, as distortion product otoacoustic emissions appeared equally affected by day or night noise exposure, in all strains and in all noise conditions. Minor differences in ribbon counts or synaptic pairing were found in CBA/Sca mice, which were inconsistent with ABR wave 1 amplitude changes. Interestingly, CORT levels peaked in CBA/Sca mice at the onset of darkness at zeitgeber time 12 reaching levels of 43.8 ng/ml, while in the CBA/CaJ and the CBA/JRj, levels were 11.9 and 15.6 ng/ml respectively and peaking 4 h earlier (zeitgeber time 8). These findings were consistent with higher period of daily rhythm in CBA/Sca mice when measured in complete darkness using running wheels (23.7 h), than in CBA/CaJ (23.45 h

关键词： 导数   数学概念   精致化教学  

摘要： 导数是横跨中学数学和高等数学的一个重要数学概念,与初等数学所涉及的一系列思想方法有着本质的区别.为促进中学生对导数本质及工具属性的认识,本文从精致化教学的角度,讨论高中导数教学中无穷小量与函数连续、导数概念、原函数与导函数的关系、函数极值、二阶导数等多个关键概念的教学处理.