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991.
Yao F Müller HG Clifford AJ Dueker SR Follett J Lin Y Buchholz BA Vogel JS 《Biometrics》2003,59(3):676-685
We present the application of a nonparametric method to performing functional principal component analysis for functional curve data that consist of measurements of a random trajectory for a sample of subjects. This design typically consists of an irregular grid of time points on which repeated measurements are taken for a number of subjects. We introduce shrinkage estimates for the functional principal component scores that serve as the random effects in the model. Scatterplot smoothing methods are used to estimate the mean function and covariance surface of this model. We propose improved estimation in the neighborhood of and at the diagonal of the covariance surface, where the measurement errors are reflected. The presence of additive measurement errors motivates shrinkage estimates for the functional principal component scores. Shrinkage estimates are developed through best linear prediction and in a generalized version, aiming at minimizing one-curve-leave-out prediction error. The estimation of individual trajectories combines data obtained from that individual as well as all other individuals. We apply our methods to new data regarding the analysis of the level of 14C-folate in plasma as a function of time since dosing of healthy adults with a small tracer dose of 14C-folic acid. A time transformation was incorporated to handle design irregularity concerning the time points on which the measurements were taken. The proposed methodology, incorporating shrinkage and data-adaptive features, is seen to be well suited for describing population kinetics of 14C-folate-specific activity and random effects, and can also be applied to other functional data analysis problems. 相似文献
992.
Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b 总被引:4,自引:0,他引:4
Zhang W Shao Y Fang D Huang J Jeon MS Liu YC 《The Journal of biological chemistry》2003,278(26):23978-23983
It was previously reported that Cbl-b associates with Crk-L in Jurkat T cells. However, the physiological significance of such association remains unclear. Here we examined a regulatory role of Cbl-b in Crk-L-C3G signaling pathway. We found that Cbl-b associates with, and induces, ubiquitin conjugation to Crk-L, which requires a functional RING finger. Cbl-b deficiency does not affect Crk-L stability, but its association with C3G. In Cbl-b-/- T cells, the interaction between Crk-L and C3G, and the activity of the small GTPase Rap1, are increased. Cbl-b-/- T cells also display increased adhesion and cell surface binding to ICAM-1, a finding that is supported by the enhanced clustering of LFA-1 in Cbl-b-/- T cells in response to TCR stimulation. Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells. 相似文献
993.
Hierarchy of polymorphic variation and desensitization permutations relative to beta 1- and beta 2-adrenergic receptor signaling 总被引:1,自引:0,他引:1
Rathz DA Gregory KN Fang Y Brown KM Liggett SB 《The Journal of biological chemistry》2003,278(12):10784-10789
Agonist-promoted desensitization of G-protein-coupled receptors results in partial uncoupling of receptor from cognate G-protein, a process that provides for rapid adaptation to the signaling environment. This property plays important roles in physiologic and pathologic processes as well as therapeutic efficacy. However, coupling is also influenced by polymorphic variation, but the relative impact of these two mechanisms on signal transduction is not known. To determine this we utilized recombinant cells expressing the human beta(1)-adrenergic receptor (beta(1)AR) or a gain-of-function polymorphic variant (beta(1)AR-Arg(389)), and the beta(2)-adrenergic receptor (beta(2)AR) or a loss-of-function polymorphic receptor (beta(2)AR-Ile(164)). Adenylyl cyclase activities were determined with multiple permutations of the possible states of the receptor: genotype, basal, or agonist stimulated and with or without agonist pre-exposure. For the beta(1)AR, the enhanced function of the Arg(389) receptor underwent less agonist-promoted desensitization compared with its allelic counterpart. Indeed, the effect of polymorphic variation on absolute adenylyl cyclase activities was such that desensitized beta(1)AR-Arg(389) signaling was equivalent to non-desensitized wild-type beta(1)AR; that is, the genetic component had as much impact as desensitization on receptor coupling. In contrast, the enhanced signaling of wild-type beta(2)AR underwent less desensitization compared with beta(2)AR-Ile(164), thus the heterogeneity in absolute signaling was markedly broadened by this polymorphism. Inverse agonist function was not affected by polymorphisms of either subtype. A general model is proposed whereby up to 10 levels of signaling by G-protein-coupled receptors can be present based on the influences of desensitization and genetic variation on coupling. 相似文献
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997.
高压氧对脑 因再灌注海马CA1区神经元调亡作用的研究 总被引:10,自引:0,他引:10
目的和方法:应用TUNEL检测技术,对沙土鼠前脑缺血20min后再灌注3d模型,用HBO治疗连续3d。观察HBO作用下海马CA1区神经元凋亡变化,研讨HBO对脑缺血再灌注损伤的疗效及其机理,为临床应用HBO治疗疾病提供理论依据。结果:沙土鼠脑缺血再灌注3d后海马CA1区大量神经元凋亡,HBO治疗组凋亡细胞数明显减少(P<0.01),并以0.25MPa HBO治疗组为佳。结论:HBO治疗对海巴神经元损伤有保护作用,减少神经元凋亡,为高压氧治疗缺血性损伤有疗效机理之一。 相似文献
998.
对武汉东湖大型围隔和围栏中的水生植被和不同形态的磷近2年的调查分析结果表明:在围隔中的水生维管束植物得到恢复、生物量明显大于对照区的情况下,水中的总磷(TP)、溶解活性磷(DRP)、颗粒性磷(PP)浓度明显低于对照区,水生维管束植物的良好生长是导致磷浓度降低的主要因素,总溶解磷(TDP)、溶解非活性磷(DNP)浓度则与对照区无显著差异;围隔(栏)及对照区中TP、PP的浓度秋高冬低,TDP浓度秋、冬季较高,春、夏季较低,DNP浓度春季较高,冬季较低;TP中PP含量约为TDP的4-6倍,DRP与DNP的含量相近或稍有差别。 相似文献
999.
Down-regulated expression of atypical PKC-binding domain deleted asip isoforms in human hepatocellular carcinomas 总被引:1,自引:0,他引:1
INTRODUCTIONCell polarity is the reflection of complex mechanisms that establish and maintain the functionally specialized regions in the plasma membrane and cytoplasm, and is fundamentally important for differentiation, proliferation, morphogenesis and other functions of simple and complicated organisms[1].Molecular mechanisms of cell polarity during animal development have been analyzed mainly in the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster[2]. In early … 相似文献
1000.
砂仁叶片光破坏的防御 总被引:18,自引:6,他引:12
报告了生长于热带林窗向阳处砂仁叶片叶绿素荧光参数的日变化,及阻止卷叶和用二硫苏糖醇(DTT)处理对它的影响.受强光照射,砂仁叶片迅速卷起.在雾天上午光强还相当弱(低于100μmol m-2s-1)时,砂仁叶片就发生光抑制,中午最重,下午当光强减弱时,光抑制逐渐得到缓解.其热耗散(qN、NPQ)随光强的升高而增加,且下午仍在缓慢增加.阻止卷叶使强光下砂仁叶片光抑制加剧,F0、NPQ升高.DTT处理也使光抑制加剧,F0升高,且使PSⅡ反应中心发生可逆失活.夜间2300各处理的荧光参数基本恢复.卷叶、叶黄素循环和PSⅡ可逆失活3种保护机制在同种植物中依次启动的现象尚属少见. 相似文献