potential mechanisms involved in resistant phenotype of MCF-7breast carcinoma cells to ionizing radiation induced apoptosis

In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage,carbon ion irradiation resulted in an approximately 1.9–2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might,at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

BRCA1 and its phosphorylation involved in caffeine-inhibitable event upstream of G2 checkpoint

Caffeine, which specifically inhibits ATM/ATR kinases, efficiently abrogates the ionizing radiation (IR)-induced G2 arrest and increases the sensitivity of various tumor cells to IR. Mechanisms for the effect of caffeine remain to be elucidated. As a target of ATM/ATR kinases, BRCA1 becomes activated and phosphorylated in response to IR. Thus, in this work, we investigated the possible role of BRCA1 in the effect of caffeine on G2 checkpoint and observed how BRCA1 phosphorylation was regulated in this process. For these purposes, the BRCA1 protein level and the phosphorylation states were analyzed by Western blotting by using an antibody against BRCA1 and phospho-specific antibodies against Ser-1423 and Ser-1524 residues in cells exposed to a combination of IR and caffeine. The results showed that caffeine down-regulated IR-induced BRCA1 expression and specifically abolished BRCA1 phosphorylation of Ser-1524, which was followed by an override of G2 arrest by caffeine. In addition, the ability of BRCA1 to transactivate p21 may be required for MCF-7 but not necessary for Hela response to caffeine. These data suggest that BRCA1 may be a potential target of caffeine. BRCA1 and its phosphorylation are most likely to be involved in the caffeine-inhibitable event upstream of G2 arrest.

BRCA1对人乳腺癌细胞辐射敏感性的影响及其作用机制研究

目的：研究肿瘤抑制子BRCA1在人乳腺癌细胞辐射抗性中的作用，并探讨其作用机制。材料和方法：利用实时细胞分析系统检测辐射对细胞存活的影响；流式细胞术检测辐射对细胞周期分布的影响；RT-PCR检测辐射导致的BRCA1、Bax和Bcl-2在 mRNA水平变化；Western blot方法检测辐射诱导的蛋白表达水平的变化； In-cell western定量检测辐射引起的蛋白表达水平的变化； AO/EB染色法检测辐射导致的细胞死亡情况。结果：第一，分别用1Gy和4Gy x射线和碳离子束辐照人乳腺癌细胞MCF-7，研究MCF-7对不同LET射线的辐射敏感性差异。结果显示，x射线组1Gy辐射导致细胞存活显著下降，4Gy辐射对细胞存活影响不明显；而碳离子束辐射对细胞生长无抑制作用。与x射线组比较，碳离子辐射诱导了更低的亚“G1”期细胞百分数和更显著的G2期阻滞现象。同时碳离子束辐射诱导BRCA1磷酸化水平和p21表达上调，Bax表达下调。以上结果表明MCF-7对辐射的耐受性与凋亡功能相关，而BRCA1 Ser-1524磷酸化作用可能参与细胞周期和凋亡的信号调控。第二，研究BRCA1在咖啡因诱导的辐射增敏效应中作用。当2mM咖啡因联合4Gy的x射线或碳离子束辐射处理MCF-7细胞后，观察到细胞存活显著下降，辐射诱导的G2期阻滞被废除，BRCA1和p21蛋白表达被抑制，而p53表达水平无明显变化。结果表明咖啡因诱导的MCF-7细胞的辐射增敏作用可能与G2期阻滞被废除相关，BRCA1可能参与该过程的信号调节。第三， 利用BRCA1功能正常的MCF-7细胞和BRCA1功能缺失的HCC1937细胞进一步研究BRCA1对细胞辐射敏感性的影响。辐射显著抑制了HCC1937细胞存活，但对MCF-7细胞存活无明显影响。与HCC1937细胞相比，辐射诱导MCF-7细胞发生显著的G2期阻滞。辐射诱导HCC1937细胞发生晚期凋亡，而MCF-7细胞则多发生早期凋亡，且MCF-7细胞凋亡数明显少于HCC1937细胞。RT-PCR检测结果显示，辐射增强了MCF-7细胞中BRCA1的mRNA 水平，抑制了Bax的mRNA 水平，对Bcl-2的影响不明显；而HCC1937细胞中Bax的mRNA表达水平则被增强。同时辐射诱导MCF-7细胞中BRCA1和p21蛋白表达增强，Bax表达下降，Bcl-2水平略有增高。而HCC1937细胞Bax表达水平增强，但p21和Bcl-2的表达水平则检测不到。这些结果表明，正常的BRCA1功能对Bcl-2的转录表达是必须的，BRCA1通过上调p21水平，下调Bax/Bcl-2影响细胞的辐射敏感性。结论： BRCA1在人乳腺癌细胞的辐射抗性发生中发挥重要作用，BRCA1通过上调p21水平诱导G2期阻滞，下调Bax/Bcl-2抑制凋亡信号，使得细胞对辐射诱导的凋亡产生抗性，最终导致细胞对辐射产生耐受性

黄河三角洲湿地生态系统的形成及其保护

通过对黄河三角洲新生湿地的野外调查,利用TM陆地卫星影像图的判读,结合黄河尾闾变动的历史资料分析,结果表明,黄河三角洲新生湿地是多泥沙的黄河淤积和海岸蚀退所形成.受区域气候、地貌、地质沉积、土壤、植被的相互作用和互相影响,形成4.5×105hm2的湿地,其中有6.84×104hm2的人工湿地.湿地生态类型随着黄河尾闾摆动和海退陆进程度而变化,自海洋向陆地依次为潮下带水生生态系统潮间带湿地生态系统潮上带盐生生态系统芦苇獐茅湿地生态系统草甸湿地生态系统陆上农田生态系统.该系统资源丰富,共有野生动物1524种,鸟类300种,鱼类1040种.石油开发和近年来黄河断流对湿地产生一定影响,应在开发利用中加强管理和保护

Sensing H2O2 with layer-by-layer assembled Fe3O4-PDDA nanocomposite film

It was found that Fe3O4 nanoparticles (Fe3O4 NPs) possess intrinsic enzyme mimetic activity similar to that found in natural peroxidase. Here, we applied Fe3O4 NPs to the construction of efficient electrochemical sensor to detect the concentration of hydrogen peroxide. The sensor was fabricated with layer-by-layer assembly of Fe3O4 NPs and poly(diallyldimethylammonium chloride) (PDDA) through the electrostatic interaction, and the multilayer film was characterized with UV-vis absorption spectra, atomic force microscopy, and cyclic voltammetry.

胶州湾生态系统数学模型与计算机模拟及优化管理对策

六十年代产生的系统生态学，在生态系统研究中使得数学模型至今都是一个必不可少的有效工具，建立数学模型已成为生态学中研究的热点。文章运用概率统计、时序分析手段及灰色系统理论，对胶州湾生态系统调查的历史资料进行初步分析，取得如下成果。1. 建立了非生物环境因子的八个静态统计模型，并分析了它们之间的相关关系，从定性、定量的角度对胶州湾非生物环境因子相互关系进行了研究，并结合实际情况对数学模型进行了解释。2. 根据历史资料及前人研究成果，把胶州湾生态系统划分为：浮游动物、浮游动物食性鱼类、植食性鱼类、底栖生物、底栖生物食性鱼类、肉食性鱼类六个子系统，并把有机质及浮游植物（初级生产力）作为系统的输入，运用灰关联度方法对子系统与生物及非生物环境因子的关系进行定量分析，排列出影响各子系统生物量变化的非生物环境因素的主次顺序，建立了相应的GM（1，N）模型，并对模型进行了残差检验，模型能较好的反映实际情况。预测了各子系统的发展特性，并结合实际情况提出了各类渔业资源管理的具体指标值，对优化子系统提供了具体参数。3. 根据胶州湾的实际情况，提出了新的数学模型 - 差分摆动模型及其建立方法。模型的意义在于可量化任意几个有关因子的数量关系，并对未能考虑到的因子，甚至一直未能被人们认识到的所有因子对这种生物作用的信息量进行量化，把生态系统中生物与非生物环境因子相互作用通过方程联系起来，并在论文中得到了验证。4. 根据灰色系统分析方法，对胶州湾生态系统进行了动态分析，建立了生态系统的量化动态模型，利用劳斯判断准则及根平面法，分析了系统的发展稳定状态，发现胶州湾生态系统周年内处于不稳定的发展状态。总之，论文运用各种数学手段从系统的角度来分析生态系统中各环境因子之间关系，并用数学模型把这种关系定量地表示出来，利用胶州湾生态系统现有资料，对胶州湾生态系统从系统的角度进行综合分析，为科学管理与合理开发胶州湾生物资源、优化胶州湾生态系统提供了意义的参考意见。

白垩纪超静磁带地球磁场古强度测定

The long-term variations in the strength of the geomagnetic field provide important constraints on the chemical-physical processes of the Earth’s interior. Especially, the intensity of the geomagnetic field during the Cretaceous normal superchron (CNS) is crucial to understand the geodynamo. But a paucity of paleointensity further limits to obtain essential knowledge interior process in the deep earth. In order to improve the experimental efficiency, this study tried to apply two new rock magnetic methods (FORC diagram and low-temperature demagnetization technique) to determine the paleointensity. First, some problems in the theory and technique in paleointensity experiments were introduced. A combined palaeomagnetic and geochronologic study was further conducted on a basaltic lava sequence at Jianchang in Liaoning Province, northeastern China. Radiometric 40Ar/39Ar dating indicates that the volcanism occurred at about 119 Ma within the marine anomaly C34n in Cretaceous normal superchron (CNS). Rock magnetic investigations show that pseudo-single domain (PSD) titanium-poor titanomagnetite is dominant in the studied lava flows. Both stepwise thermal and alternating field demagnetizations isolate the well-defined normal characteristic remanent magnetization (ChRM) in three independent lava flows with a mean direction of D/I = 6.0/51.9 degree(a95 = 12.3degree). Palaeointensity was determined using the modified Thellier method with systematic partial thermoremanent magnetization (pTRM) checks on total 72 samples, but only 10 samples exhibit ideal linear behavior on the Arai-plot in the temperature interval of 300-560 C and yield an average paleointensity of (25.8+/-1.4)uT. In addition, slopes of the line defined by the initial and the final points on the Arai-plot for the other 18 samples with characteristic PSD features give an average paleointensity estimation value of (24.8+/-1.9)uT. The consistency of these two approaches confidently demonstrates the fidelity of our results. The overall mean field strength determined using both approaches are thus estimated to be (25.2+/-0.7 )uT. This value corresponds to the virtual dipole magnetic moments (VDM) of (4.5+/-0.1)E22 Am^2, which is about half of the value of present field. This finding suggests that palaeointensity just at the onset of the CNS is characterized by a weak magnetic field.

Series Elastic Actuators

This thesis presents the design, construction, control and evaluation of a novel force controlled actuator. Traditional force controlled actuators are designed from the premise that "Stiffer is better''. This approach gives a high bandwidth system, prone to problems of contact instability, noise, and low power density. The actuator presented in this thesis is designed from the premise that "Stiffness isn't everything". The actuator, which incorporates a series elastic element, trades off achievable bandwidth for gains in stable, low noise force control, and protection against shock loads. This thesis reviews related work in robot force control, presents theoretical descriptions of the control and expected performance from a series elastic actuator, and describes the design of a test actuator constructed to gather performance data. Finally the performance of the system is evaluated by comparing the performance data to theoretical predictions.

Providing Soft Bandwidth Guarantees Using Elastic TCP-based Tunnels

The best-effort nature of the Internet poses a significant obstacle to the deployment of many applications that require guaranteed bandwidth. In this paper, we present a novel approach that enables two edge/border routers-which we call Internet Traffic Managers (ITM)-to use an adaptive number of TCP connections to set up a tunnel of desirable bandwidth between them. The number of TCP connections that comprise this tunnel is elastic in the sense that it increases/decreases in tandem with competing cross traffic to maintain a target bandwidth. An origin ITM would then schedule incoming packets from an application requiring guaranteed bandwidth over that elastic tunnel. Unlike many proposed solutions that aim to deliver soft QoS guarantees, our elastic-tunnel approach does not require any support from core routers (as with IntServ and DiffServ); it is scalable in the sense that core routers do not have to maintain per-flow state (as with IntServ); and it is readily deployable within a single ISP or across multiple ISPs. To evaluate our approach, we develop a flow-level control-theoretic model to study the transient behavior of established elastic TCP-based tunnels. The model captures the effect of cross-traffic connections on our bandwidth allocation policies. Through extensive simulations, we confirm the effectiveness of our approach in providing soft bandwidth guarantees. We also outline our kernel-level ITM prototype implementation.

Safe Compositional Network Sketches: The Formal Framework

NetSketch is a tool for the specification of constrained-flow applications and the certification of desirable safety properties imposed thereon. NetSketch is conceived to assist system integrators in two types of activities: modeling and design. As a modeling tool, it enables the abstraction of an existing system while retaining sufficient information about it to carry out future analysis of safety properties. As a design tool, NetSketch enables the exploration of alternative safe designs as well as the identification of minimal requirements for outsourced subsystems. NetSketch embodies a lightweight formal verification philosophy, whereby the power (but not the heavy machinery) of a rigorous formalism is made accessible to users via a friendly interface. NetSketch does so by exposing tradeoffs between exactness of analysis and scalability, and by combining traditional whole-system analysis with a more flexible compositional analysis. The compositional analysis is based on a strongly-typed Domain-Specific Language (DSL) for describing and reasoning about constrained-flow networks at various levels of sketchiness along with invariants that need to be enforced thereupon. In this paper, we define the formal system underlying the operation of NetSketch, in particular the DSL behind NetSketch's user-interface when used in "sketch mode", and prove its soundness relative to appropriately-defined notions of validity. In a companion paper [6], we overview NetSketch, highlight its salient features, and illustrate how it could be used in two applications: the management/shaping of traffic flows in a vehicular network (as a proxy for CPS applications) and in a streaming media network (as a proxy for Internet applications).

Scientism and instrumentalism After the Bomb: Dr Strangelove, End Zone, Crash and The Wire

This thesis argues that through the prism of America’s Cold War, scientism has emerged as the metanarrative of the postnuclear age. The advent of the bomb brought about a new primacy for mechanical and hyperrational thinking in the corridors of power not just in terms of managing the bomb itself but diffusing this ideology throughout the culture in social sciences, economics and other such institutional systems. The human need to mitigate or ameliorate against the chaos of the universe lies at the heart of not just religious faith but in the desire for perfect control. Thus there has been a transference of power from religious faith to the apparent material power of science and technology and the terra firma these supposedly objective means supply. The Cold War, however was a highly ideologically charged opposition between the two superpowers, and the scientific methodology that sprang forth to manage the Cold War and the bomb, in the United States, was not an objective scientific system divorced from the paranoia and dogma but a system that assumed a radically fundamentalist idea of capitalism. This is apparent in the widespread diffusion of game theory throughout Western postindustrial institutions. The inquiry of the thesis thus examines the texts that engage and criticise American Cold War methodology, beginning with the nuclear moment, so to speak, and Dr Strangelove’s incisive satire of moral abdication to machine processes. Moving on chronologically, the thesis examines the diffusion of particular kinds of masculinity and sexuality in postnuclear culture in Crash and End Zone and finishing up its analysis with the ethnographic portrayal of a modern American city in The Wire. More than anything else, the thesis wishes to reveal to what extent this technocratic consciousness puts pressure on language and on binding narratives.