Quantile regression models with multivariate failure time data

As an alternative to the mean regression model, the quantile regression model has been studied extensively with independent failure time data. However, due to natural or artificial clustering, it is common to encounter multivariate failure time data in biomedical research where the intracluster correlation needs to be accounted for appropriately. For right-censored correlated survival data, we investigate the quantile regression model and adapt an estimating equation approach for parameter estimation under the working independence assumption, as well as a weighted version for enhancing the efficiency. We show that the parameter estimates are consistent and asymptotically follow normal distributions. The variance estimation using asymptotic approximation involves nonparametric functional density estimation. We employ the bootstrap and perturbation resampling methods for the estimation of the variance-covariance matrix. We examine the proposed method for finite sample sizes through simulation studies, and illustrate it with data from a clinical trial on otitis media.     

中性内肽酶及其抑制剂在心血管疾病过程中的作用

中性内肽酶是一种属于Ⅱ型跨膜蛋白的肽类内切酶,在肽链的氨基端水解疏水氨基酸肽键,灭活心钠素、肾上腺髓质素、血管紧张素、内皮素等心血管活性肽,在高血压病、心力衰竭、动脉粥样硬化和休克等心血管疾病的发病过程中发挥重要作用。     

Using pseudo-amino acid composition and support vector machine to predict protein structural class

As a result of genome and other sequencing projects, the gap between the number of known protein sequences and the number of known protein structural classes is widening rapidly. In order to narrow this gap, it is vitally important to develop a computational prediction method for fast and accurately determining the protein structural class. In this paper, a novel predictor is developed for predicting protein structural class. It is featured by employing a support vector machine learning system and using a different pseudo-amino acid composition (PseAA), which was introduced to, to some extent, take into account the sequence-order effects to represent protein samples. As a demonstration, the jackknife cross-validation test was performed on a working dataset that contains 204 non-homologous proteins. The predicted results are very encouraging, indicating that the current predictor featured with the PseAA may play an important complementary role to the elegant covariant discriminant predictor and other existing algorithms.     

海南岛早志留世晚期腕足类Xinanospirifer的发现--兼论南好组

海南岛保亭县毛感乡南兵至南好公路边南好组以往被确认为下石炭统岩关阶 ,并认为与其下的上志留统足赛岭组呈角度不整合接触。著者最近在该剖面南好组中发现兰多维列世特里奇期晚期 (LateTelychian)Xi nanospirifer腕足动物群和三叶虫Latiproetuscf.latilimbatus,证明久归于下石炭统岩关阶南好组的地质时代应改归于早志留世 (Llandoverian) ;海南岛地区在早志留世明显属于扬子地台区的范畴 ;从地质时间上还暗示南好组与其下伏的足赛岭组不可能存在角度不整合接触 ;     

Application of proteomics in the study of tumor metastasis

Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive.The identification of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clinical management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental approaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing methodologies will continue to extend its application in studying cancer metastasis.     

Scavenger receptor class B type I reduces cholesterol absorption in cultured enterocyte CaCo-2 cells

Scavenger receptor class B type I (SR-BI) mediates selective uptake of cholesteryl esters from HDL as well as efflux of cellular free cholesterol to HDL. It is unclear whether the receptor is involved in intestinal cholesterol absorption. We addressed this issue by studying [3H]cholesterol flux in differentiated CaCo-2 cells incubated at their apical side with mixed taurocholate/phosphatidylcholine/cholesterol micelles. Biotinylation and HDL binding experiments showed predominant apical expression of endogenous and overexpressed SR-BI. Mixed micellar cholesterol saturation affected the magnitude and direction of cholesterol flux with significant net uptake only from supersaturated micelles and net efflux from unsaturated micelles. Incubation with micelles that depleted cellular cholesterol resulted in a decrease of SR-BI protein, whereas incubation with cholesterol-loading micelles resulted in a significant increase of SR-BI protein. Apical cholesterol uptake by CaCo-2 cells was increased in the presence of a SR-BI-blocking antibody and by partial inhibition of SR-BI expression with small inhibitory RNA. Adenovirus-mediated overexpression of apical SR-BI did not affect cholesterol uptake but stimulated apical cholesterol efflux, even to supersaturated mixed micelles. Partial inhibition of SR-BI with small inhibitory RNA reduced apical cholesterol efflux. Our data argue against a direct role for SR-BI in micellar cholesterol uptake. However, SR-BI might be involved in cholesterol absorption by facilitating cholesterol efflux to micelles.     

基因型和胚龄对小麦未成熟胚离体培养反应的影响

本文对34种基因型的小麦未成熟胚在离体培养中的反应进行了比较。结果表明,94％的供试基因型愈伤组织诱导率都可达到80％以上,若排除供体植株环境条件的不同和接种过程中的人为因素可能造成的影响,不同基因型的愈伤组织诱导率看来没有根本的差异。愈伤组织分化率因基因型的不同变动在0—60％之间,平均为32.7％。虽然同一基因型的盾片愈伤组织分化率在不同年份中有所不同,但是愈伤组织是否具有再生能力?看来是个稳定的遗传性状。因此小麦未成熟胚对愈伤组织诱导的反应和愈伤组织的再生能力可能具有不同的遗传基础。本文的结果还表明,虽然最适于培养的未成熟胚的大小为1毫米左右,伹小至0.3毫米的未成熱胚仍能以几乎100％的频率形成愈伤组织,60％左右的愈伤组织能分化出再生檀株,只是所需的时间比1毫米左右的胚较长。     

表达新城疫病毒HN基因的重组火鸡疱疹病毒的构建

应用聚合酶链反应技术,用设计带有限制性酶切位点的引物,特异地扩增从起始密码子开始的１ ．８ ｋｂ 新城疫病毒（ Ｎ Ｄ Ｖ） 血凝素神经氨酸酶（ Ｈ Ｎ） 基因开放式阅读框,然后插入ｐ Ｔ Ｋ２ Ｂ 的 Ｎｈｅ Ⅰ位点,构建了含 Ｎ Ｄ Ｖ Ｈ Ｎ 基因的插入载体ｐ Ｔ Ｋ Ｈ Ｎ１ 和ｐ Ｔ Ｋ Ｈ Ｎ２ ,再与感染火鸡疱疹病毒（ Ｈ Ｖ Ｔ） 细胞的总 Ｄ Ｎ Ａ 共转染鸡胚成纤维细胞（ Ｃ Ｅ Ｆ） ,经有限稀释法和 Ｄｏｔｂｌｏｔ 筛选,得到含有 Ｈ Ｎ 基因的重组体ｒ Ｈ Ｖ Ｔ１ 和ｒ Ｈ Ｖ Ｔ２ 。经组织培养传代和 Ｗｅｓｔｅｒｎ ｂｌｏｔ 分析,表明重组体在感染细胞中表达了 Ｈ Ｎ 蛋白。重组体在 Ｃ Ｅ Ｆ 上的生长特性与亲本病毒相同,且在连续传代过程中保持稳定。为国内新城疫基因工程疫苗研制奠定了基础。     

A role for JNK-paxillin signaling in cell migration

Recently, we and others demonstrated that JNK is essential for cell migration in a number of cell types. We also showed that JNK phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in vivo. Moreover, phosphorylation of Ser 178 on paxillin is essential for cell migration and involved in modulating cell adhesions. A model is proposed to depict the role of JNK-paxillin signaling in cell migration.     

Prediction of tyrosine sulfation with mRMR feature selection and analysis

Protein tyrosine sulfation is a ubiquitous post-translational modification (PTM) of secreted and transmembrane proteins that pass through the Golgi apparatus. In this study, we developed a new method for protein tyrosine sulfation prediction based on a nearest neighbor algorithm with the maximum relevance minimum redundancy (mRMR) method followed by incremental feature selection (IFS). We incorporated features of sequence conservation, residual disorder, and amino acid factor, 229 features in total, to predict tyrosine sulfation sites. From these 229 features, 145 features were selected and deemed as the optimized features for the prediction. The prediction model achieved a prediction accuracy of 90.01% using the optimal 145-feature set. Feature analysis showed that conservation, disorder, and physicochemical/biochemical properties of amino acids all contributed to the sulfation process. Site-specific feature analysis showed that the features derived from its surrounding sites contributed profoundly to sulfation site determination in addition to features derived from the sulfation site itself. The detailed feature analysis in this paper might help understand more of the sulfation mechanism and guide the related experimental validation.