An acylation cycle regulates localization and activity of palmitoylated Ras isoforms

We show that the specific subcellular distribution of H- and Nras guanosine triphosphate-binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus. Depalmitoylation redistributes farnesylated Ras in all membranes, followed by repalmitoylation and trapping of Ras at the Golgi, from where it is redirected to the PM via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalization. The de/reacylation cycle also initiates Ras activation at the Golgi by transport of PM-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors.     

Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans

The activity of an oncoprotein and the secretion of a pheromone can be affected by an unusual protein modification. Specifically, posttranslational modification of yeast a-factor and Ras protein requires an intermediate of the cholesterol biosynthetic pathway. This modification is apparently essential for biological activity. Studies of yeast mutants blocked in sterol biosynthesis demonstrated that the membrane association and biological activation of the yeast Ras2 protein require mevalonate, a precursor of sterols and other isoprenes such as farnesyl pyrophosphate. Furthermore, drugs that inhibit mevalonate biosynthesis blocked the in vivo action of oncogenic derivatives of human Ras protein in the Xenopus oocyte assay. The same drugs and mutations also prevented the posttranslational processing and secretion of yeast a-factor, a peptide that is farnesylated. Thus, the mevalonate requirement for Ras activation may indicate that attachment of a mevalonate-derived (isoprenoid) moiety to Ras proteins is necessary for membrane association and biological function. These observations establish a connection between the cholesterol biosynthetic pathway and transformation by the ras oncogene and offer a novel pharmacological approach to investigating, and possibly controlling, ras-mediated malignant transformations.     

The spread of Ras activity triggered by activation of a single dendritic spine

In neurons, individual dendritic spines isolate N-methyl-d-aspartate (NMDA) receptor-mediated calcium ion (Ca2+) accumulations from the dendrite and other spines. However, the extent to which spines compartmentalize signaling events downstream of Ca2+ influx is not known. We combined two-photon fluorescence lifetime imaging with two-photon glutamate uncaging to image the activity of the small guanosine triphosphatase Ras after NMDA receptor activation at individual spines. Induction of long-term potentiation (LTP) triggered robust Ca2+-dependent Ras activation in single spines that decayed in approximately 5 minutes. Ras activity spread over approximately 10 micrometers of dendrite and invaded neighboring spines by diffusion. The spread of Ras-dependent signaling was necessary for the local regulation of the threshold for LTP induction. Thus, Ca2+-dependent synaptic signals can spread to couple multiple synapses on short stretches of dendrite.     

A cytoplasmic protein inhibits the GTPase activity of H-Ras in a phospholipid-dependent manner

A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation.     

黄河流域生态空间网络特征

  目的  黄河流域在生态环境保护中有着举足轻重的地位,为了有效地应对城市快速发展所带来的生态环境问题,本文针对黄河流域构建了生态空间网络,以保护生物多样性、减缓景观格局破碎化。  方法  以黄河流域为研究对象,基于土地利用数据、生态斑块面积周长、归一化植被指数(NDVI)、改进的归一化水体指数(MNDWI)和平均斑块分维数,选取了生态源地;利用GIS空间分析和MCR模型算法构建最小累积生态阻力面,提取出潜在生态廊道和生态节点;最终得到由生态源地和潜在生态廊道组成的黄河流域潜在生态空间网络并对其进行鲁棒性分析。  结果  （1）黄河流域潜在生态空间网络由294块生态源地和369条潜在生态廊道组成。（2）生态源地主要土地利用类型为林地、草地和水域,主要分布在东北部和西南部,东南部也有零星分布。（3）生态廊道在东北部和西南部密度较大,生态空间网络结构复杂,在小块生态源地之间长度较长,对研究区生态环境发挥关键作用。（4）网络中共提取125个生态节点并使用matlab进行模拟攻击测试其鲁棒性,总体上随机攻击下生态空间网络的恢复鲁棒性优于恶意攻击,连接鲁棒性在攻击一定数量的节点后呈现大幅度上涨,网络结构崩溃。  结论  本文基于MCR模型构建黄河流域的潜在生态空间网络并对其进行了拓扑结构分析,为生态空间网络优化提供重要借鉴意义,为促进黄河流域高质量发展、提高黄河流域的生态文明建设水平提供理论指导。      

Activation of the cellular proto-oncogene product p21Ras by addition of a myristylation signal

The 21-kD proteins encoded by ras oncogenes (p21Ras) are modified covalently by a palmitate attached to a cysteine residue near the carboxyl terminus. Changing cysteine at position 186 to serine in oncogenic forms produces a nonpalmitylated protein that fails to associate with membranes and does not transform NIH 3T3 cells. Nonpalmitylated p21Ras derivatives were constructed that contained myristic acid at their amino termini to determine if a different form of lipid modification could restore either membrane association or transforming activity. An activated p21Ras, altered in this way, exhibited both efficient membrane association and full transforming activity. Surprisingly, myristylated forms of normal cellular Ras were also transforming. This demonstrates that Ras must bind to membranes in order to transmit a signal for transformation, but that either myristate or palmitate can perform this role. However, the normal function of cellular Ras is diverted to transformation by myristate and therefore must be regulated ordinarily by some unique property of palmitate that myristate does not mimic. Myristylation thus represents a novel mechanism by which Ras can become transforming.     

网络仿真实验系统的研究与实现

本文综合利用Sniffer协议分析技术,开发出一套高效实用的计算机网络实验系统.在构建一种新的基于Sniffer计算机网络协议分析模型上,系统通过截获各种协议数据包来实现计算机网络协议的分析,并在协议分析的基础上确定网络故障、病毒等,给出了常用的网络实验的主要内容及使用的主要工具,并对其中的一个实验进行了详细说明.     

A cytosolic protein catalyzes the release of GDP from p21ras

The rate of release of guanine nucleotides from the ras proteins (Ras) is extremely slow in the presence of Mg2+. It seemed likely, therefore that a factor might exist to accelerate the release of guanosine diphosphate (GDP), and hence the exchange of GDP for guanosine triphosphate (GTP). Such a factor has now been discovered in rat brain cytosol. Brain cytosol was found to catalyze, by orders of magnitude, the release of guanine nucleotides from recombinant v-H-Ras protein bound with [alpha-32P]GDP. This effect occurred even in the presence of a large excess of Mg2+, but was destroyed by heat or by incubation of the cytosol for an hour at 37 degrees C in the absence of phosphatase inhibitors. The effect was observed with either v-H-Ras or c-H-Ras, but not with p25rab3A, a small G protein with about 30% similarity to Ras. The effect could not be mimicked by addition of recombinant Ras-GAP or purified GEF, a guanine nucleotide exchange factor involved in the regulation of eukaryotic protein synthesis. By gel filtration chromatography, the factor appears to possess a molecular size between 100,000 and 160,000 daltons. This protein (Ras-guanine nucleotide-releasing factor, or Ras-GRF) may be involved in the activation of p21ras.     

基于社会网络分析的本科生社会科学潜在阅读兴趣小组挖掘探析——以中国药科大学为例

[目的/意义]自政府工作报告连续6年都提到全民阅读以来,阅读推广工作在全社会进行了全面开展。高校作为开展全民阅读的重要场所,在现代技术快速发展的背景下,急需适应时代发展的阅读推广的创新实践,为阅读的精准推广研究与实践提供有益参考。[方法/过程]本文基于社会网络分析技术,从汇文系统中下载中国药科大学的本科生的借阅数据,以UCINET计算该网络的分派状态,对本科生社会科学潜在阅读兴趣小组进行挖掘探析。[结果/结论]应用社会网络分析技术对本科生阅读数据进行分析后,可形成以本科生兴趣为核心的阅读小组,并在此基础上提出了精准阅读推广策略,提出建立复杂网络理论挖掘潜在阅读团队的模型,研究本科生阅读团队的内在动力机制等愿景。     

基于神经网络的机器人驱动系统数学模型辨识

以轮式移动机器人驱动系统为主要研究对象,提出一种基于神经网络的分析与试验相结合的建模方法。该方法在分析理想直流电动机数学模型的基础上,采用串一并行辨识结构的神经网络确定系统输出与输入的关系,实现了机器人驱动系统的数学模型辨识。最后,通过试验证明了该方法的有效性,为未采工、农业等领域机器人的精确运动和动力控制的研究提供了技术支持。     

多元目标导向下的成都中心城区绿地生态网络构建

基于形态学空间格局分析（MSPA）方法和景观连通性指数,以成都市三环内区域为研究对象,筛选研究区内维持景观连通性最重要的核心斑块作为绿地网络的生态源地;耦合最小累积阻力模型（MCR）,最小成本路径方法和重力模型,提取研究区内重要生态廊道,利用中介中心度识别踏脚石斑块,构建研究区优化的绿地生态网络。结果表明:利用MSPA方法可识别研究区内景观结构的核心区及连接桥区;利用景观连通性指数可筛选出具有重要连通性的12个核心绿地斑块作为生态源地。基于MCR模型与最小路径方法识别出的潜在绿地生态网络表明研究区南部、北部以及西南部存在生态廊道,但密集程度较小,东、西部区域生态廊道较少,生态网络结构完善度较差。利用绿地斑块的中介作用选取包括沙河公园在内的13个踏脚石斑块可构建出较为合理的研究区绿地生态网络。相比于其他城市绿地生态网络构建技术,该方法更科学,对城市绿地生态网络优化也更具参考和借鉴意义。     

Precipitation Fluctuations over Northern Hemisphere Land Areas Since the Mid-19th Century

An extensive array of measurements extending back to the mid-19th century was used to investigate large-scale changes in precipitation over Northern Hemisphere land areas. Significant increases in mid-latitude precipitation and concurrent decreases in low-latitude precipitation have occurred over the last 30 to 40 years. Although these large-scale trends are consistent with general circulation model projections of precipitation changes associated with doubled concentrations of atmospheric carbon dioxide, they should be viewed as defining large-scale natural climatic variability. Additional work to refine regional variations and address potential network inhomogeneitics is needed. This study attempts to show secular precipitation fluctuations over hemispheric and continental-scale areas of the Northern Hemisphere.     

基于Internet流媒体技术在图书馆视频资源服务中应用研究

重点介绍如何利用现有的资源和技术来构建图书馆的流媒体视频资源服务平台,给出当前情况下可行的方案,并对各个方案进行分析探究,挖掘潜在的动力以充分利用网络与视频资源。通过对各种网络视频媒体的格式和编码分析,综合用户的视觉体验,为不同用户提供优质的视频资源服务。     

浙江省慈溪市宗汉街道城镇绿地生态网络构建

以浙江省慈溪市宗汉街道为试验区,应用地理理信息系统(GIS)技术和景观格局指数方法,分析试验区景观格局特征,结合景观中心度指标节点度和紧密度,确定了城镇区核心绿地斑块,并划分为中心节点、关键节点及基本节点3种类型。运用生态适宜性分析方法和最小费用距离模型,构建了城镇区绿地系统潜在的生态廊道。结果表明:城镇区有53个绿地斑块,构成了城镇区绿地生态网络节点的核心;规划的14条潜在生态廊道能很好地结合绿地资源分布特点,连通城镇区核心绿地斑块,构建城镇区生态绿地网络系统。通过综合运用景观格局指数、最小费用距离模型、景观中心度评价等方法,可以定量地评价城镇绿地系统现状,优化城镇生态绿地网络,为城镇绿地生态网络规划与管理提供科学的参考依据。图5表3参17     

基于复杂网络理论的生态空间优化

  目的  快速的城市化发展导致景观破碎化和生态空间网络的破坏，因此合理构建生态空间网络可以促进生态源地之间能量的流动，有效缓解生态环境的恶化。  方法  以松花江流域为研究对象，基于土地利用数据提取生态源地，运用GIS空间分析技术和MCR模型，筛选生态源地及潜在生态廊道；其次，基于复杂网络方法计算生态源地“度”，运用引力模型计算松花江流域潜在生态廊道“边权”，依据复杂网络中“边权”和“度”得到研究区生态源地“权重”；最后，通过权?度相关性对研究区生态空间网络进行模拟增边优化，分析生态空间网络鲁棒性。  结果  （1）松花江流域生态空间网络由450个生态源地和1 019条潜在生态廊道组成。（2）在松花江流域生态空间网络中，齐齐哈尔市、大庆市、松原市生态源地斑块聚集度低，生态廊道结构简单,呼伦贝尔市、牡丹江市斑块聚集度高，生态空间网络错综复杂。研究区生态空间网络出现两极分化，生态环境亟需优化。（3）基于复杂网络理论，对松花江流域进行模拟增边优化。共识别增边节点20个，模拟增边24条，模拟增边优化后，网络连接鲁棒性有了明显的增强，松花江流域生态空间网络连通性以及抗干扰能力有很大提升。  结论  基于MCR模型构建生态空间网络，运用复杂网络理论对松花江流域进行增边优化，提升生态空间网络的鲁棒性，为松花江流域生态空间格局优化奠定了理论基础。      

基于MATLAB神经网络的温室草皮腾发量预测研究

[目的]明确基于MATLAB的BP神经网络预测温室草皮腾发量的可行性。[方法]在9月温室实测气象资料的基础上,对温室内的平均气温、相对湿度、光照强度和草皮日腾发量(ET)进行回归分析,建立了BP网络ET预报模型(BP-ET)。[结果]气温、光照强度与草皮腾发量呈显著正相关(P<0.05),相对湿度与草皮腾发量呈显著负相关(P<0.05)。BP神经网络模型具有极高的拟合精度,9月资料检验预报模型的平均相对误差为5.58%,模拟与检验均有很高的拟合精度。BP网络可以用于草皮日腾发量的预测,是对传统草皮日腾发量计算的补充。[结论]该研究为气象数据缺测条件下温室草皮日腾发量的估算提供了新思路。     

风速风向的解算方法研究

首先分析了影响广东省第三产业发展的主要因素，指出由于上述因素相互制约、相互影响，导致第三产业的发展呈现出高度的非线性特征，并使得单一的预测模型在预测效果和泛化能力方面难以胜任.在此基础上，提出了基于神经网络集成的组合预测模型，对广东省第三产业的发展进行预测，阐述了算法的基本原理和数据处理流程，实证分析表明：基于神经网络集成的组合预测模型要比单一预测模型的预测精度高.     

基于优化卷积神经网络的玉米螟虫害图像识别

【目的】随着人工智能和大数据技术的不断发展,针对常规玉米虫害识别方法存在的准确率和效率低等问题,本文提出了一种基于改进GoogLeNet卷积神经网络模型的玉米螟虫害图像识别方法。【方法】首先通过迁移学习将GoogLeNet的Inception-v4网络结构知识转移到玉米螟Pyrausta nubilalis虫害识别的任务上,构建模型的训练方式;然后通过数据增强技术对玉米螟虫图像进行样本扩充,得到神经网络训练模型的数据集;同时利用Inception模块拥有多尺度卷积核提取多尺度玉米螟虫害分布特征的能力构建网络模型,并在试验过程中对激活函数、梯度下降算法等模型参数进行优化;最后引入批标准化(BN)操作加速优化模型网络训练,并将该模型运用到玉米螟虫害识别中。【结果】基于TensorFlow框架下的试验结果表明,优化后的神经网络算法对玉米螟虫害图像平均识别准确率达到了96.44%。【结论】基于优化的卷积神经网络识别模型具有更强的鲁棒性和适用性,可为玉米等农作物虫害识别、智能诊断提供参考。