Youden Index and optimal cut-point estimated from observations affected by a lower limit of detection

The receiver operating characteristic (ROC) curve is used to evaluate a biomarker's ability for classifying disease status. The Youden Index (J), the maximum potential effectiveness of a biomarker, is a common summary measure of the ROC curve. In biomarker development, levels may be unquantifiable below a limit of detection (LOD) and missing from the overall dataset. Disregarding these observations may negatively bias the ROC curve and thus J. Several correction methods have been suggested for mean estimation and testing; however, little has been written about the ROC curve or its summary measures. We adapt non-parametric (empirical) and semi-parametric (ROC-GLM [generalized linear model]) methods and propose parametric methods (maximum likelihood (ML)) to estimate J and the optimal cut-point (c *) for a biomarker affected by a LOD. We develop unbiased estimators of J and c * via ML for normally and gamma distributed biomarkers. Alpha level confidence intervals are proposed using delta and bootstrap methods for the ML, semi-parametric, and non-parametric approaches respectively. Simulation studies are conducted over a range of distributional scenarios and sample sizes evaluating estimators' bias, root-mean square error, and coverage probability; the average bias was less than one percent for ML and GLM methods across scenarios and decreases with increased sample size. An example using polychlorinated biphenyl levels to classify women with and without endometriosis illustrates the potential benefits of these methods. We address the limitations and usefulness of each method in order to give researchers guidance in constructing appropriate estimates of biomarkers' true discriminating capabilities.     

Resampling-based empirical Bayes multiple testing procedures for controlling generalized tail probability and expected value error rates: focus on the false discovery rate and simulation study

This article proposes resampling-based empirical Bayes multiple testing procedures for controlling a broad class of Type I error rates, defined as generalized tail probability (gTP) error rates, gTP (q,g) = Pr(g (V(n),S(n)) > q), and generalized expected value (gEV) error rates, gEV (g) = E [g (V(n),S(n))], for arbitrary functions g (V(n),S(n)) of the numbers of false positives V(n) and true positives S(n). Of particular interest are error rates based on the proportion g (V(n),S(n)) = V(n) /(V(n) + S(n)) of Type I errors among the rejected hypotheses, such as the false discovery rate (FDR), FDR = E [V(n) /(V(n) + S(n))]. The proposed procedures offer several advantages over existing methods. They provide Type I error control for general data generating distributions, with arbitrary dependence structures among variables. Gains in power are achieved by deriving rejection regions based on guessed sets of true null hypotheses and null test statistics randomly sampled from joint distributions that account for the dependence structure of the data. The Type I error and power properties of an FDR-controlling version of the resampling-based empirical Bayes approach are investigated and compared to those of widely-used FDR-controlling linear step-up procedures in a simulation study. The Type I error and power trade-off achieved by the empirical Bayes procedures under a variety of testing scenarios allows this approach to be competitive with or outperform the Storey and Tibshirani (2003) linear step-up procedure, as an alternative to the classical Benjamini and Hochberg (1995) procedure.     

The APC/C subunit Cdc16/Cut9 is a contiguous tetratricopeptide repeat superhelix with a homo-dimer interface similar to Cdc27

The anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase responsible for controlling cell cycle transitions, is a multisubunit complex assembled from 13 different proteins. Numerous APC/C subunits incorporate multiple copies of the tetratricopeptide repeat (TPR). Here, we report the crystal structure of Schizosaccharomyces pombe Cut9 (Cdc16/Apc6) in complex with Hcn1 (Cdc26), showing that Cdc16/Cut9 is a contiguous TPR superhelix of 14 TPR units. A C-terminal block of TPR motifs interacts with Hcn1, whereas an N-terminal TPR block mediates Cdc16/Cut9 self-association through a homotypic interface. This dimer interface is structurally related to the N-terminal dimerization domain of Cdc27, demonstrating that both Cdc16/Cut9 and Cdc27 form homo-dimers through a conserved mechanism. The acetylated N-terminal Met residue of Hcn1 is enclosed within a chamber created from the Cut9 TPR superhelix. Thus, in complex with Cdc16/Cut9, the N-acetyl-Met residue of Hcn1, a putative degron for the Doa10 E3 ubiquitin ligase, is inaccessible for Doa10 recognition, protecting Hcn1/Cdc26 from ubiquitin-dependent degradation. This finding may provide a structural explanation for a mechanism to control the stoichiometry of proteins participating in multisubunit complexes.     

能量对香石竹切花在瓶插期间呼吸电子途径的影响

采用外加0.1 mmol/L ATP或0.5 mmol/L二硝基苯酚(DNP)的方法,研究了香石竹(Dianthus caryophyllus L.)切花在25±1℃和80%～90%相对湿度下瓶插期间呼吸电子传递途径的变化情况.结果表明,香石竹切花在瓶插7 d时的呼吸速率达到高峰;ATP处理明显加快切花的呼吸速率,在瓶插7 d时呼吸速率高峰值较对照(未用ATP处理)升高1倍.细胞色素途径与总呼吸活性存在显著正相关.细胞色素途径占总呼吸的比重在切花瓶插4 d后上升,并且线粒体电子传递主要依靠细胞色素主路途径进行.经ATP处理后香石竹切花的交替呼吸途径的容量、实际运行活性和运行系数明显增加;交替呼吸途径占总呼吸活性比重在瓶插4 d后迅速上升,并且交替呼吸途径容量与总呼吸活性存在显著正相关.而DNP处理则降低交替呼吸途径容量.这说明外源ATP处理加强了香石竹切花在整个瓶插期间的呼吸作用,增加了呼吸速率的高峰值,提高了抗氰呼吸作用.     

A mutation in the gene involved in sister chromatid separation causes a defect in nuclear mRNA export in fission yeast

Fission yeast ptr4-1 is one of the mRNA transport mutants that accumulate poly(A)(+) RNA in the nuclei at the nonpermissive temperature. We cloned the ptr4(+) gene and found that it is identical with the cut1(+) gene essential for chromosome segregation during mitosis. ptr4/cut1 has no defects in nucleocytoplasmic transport of a protein, indicative of a specific blockage of mRNA export by this mutation. A mutant of Cut2p cooperating with Cut1p in sister chromatid separation also showed defective mRNA export at the nonpermissive temperature. Our results suggest a novel linkage between the cell division cycle and nuclear mRNA export in eukaryotic cells.     

The exploitation of megafauna during the earliest peopling of the Americas: An examination of nineteenth-century fossil collections

This paper describes human-modified bones originally from the Pampas region, and that form part of nineteenth-century fossil collections of native fauna. We describe the morphological and configurational features of the marks, relate them to the various stages in the butchering process, and discuss access type. An examination of various different American sites is used to interpret this evidence at a coarse-grained level. Although these collections are more biased than current archaeological materials with regard to their sedimentary origin and previous handling, the application of modern technology has allowed us to obtain new data. Therefore, despite their complex history, these artefacts can be incorporated into the broader body of modern archaeological research. This type of study adds new value to our historic heritage and underscores its usefulness in modern enquiries, in this case, related to the topic of how Homo sapiens interacted with the native fauna in the southern Cone of South America.     

日光温室切花郁金香花期与外观品质预测模型

光温是影响花卉作物花期和外观品质的重要环境因子。本文目的是建立日光温室切花郁金香花期与外观品质预测模型,以期通过调节种植期和种植密度,实现日光温室切花郁金香生产的光温优化调控。本研究以郁金香品种世界珍爱(Tulip gesneriana cv ‘World Favorite’)和金检阅(Tulip gesneriana cv ‘Golden Parade’)为试材,通过不同种植期和不同密度的栽培试验,定量分析了种植期和密度对郁金香发育进程及外观品质动态的影响。在此基础上,以单株吸收辐热积(Photo-thermal Index,PTI)为尺度,建立了日光温室切花郁金香花期与外观品质预测模型,并用独立的试验数据对模型进行了检验。结果表明,模型对郁金香花期和各外观品质指标的预测效果较好。模型对各生育时期的预测值与实测值之间的决定系数R2为0.95,对萌芽期、展叶期、现蕾期和采收期的预测值与实测值的回归估计标准误RMSE分别为0.7、1.3、2.9和1天。模型对株高、展叶数、茎基长度、茎基粗度、花颈长度、花颈粗度、花蕾长度和花蕾直径的预测值与实测值之间R2分别为0.97、0.97、0.98、0.98、0.98、0.97、0.98和0.97,RMSE分别为30.8mm、0.2、3.5mm、0.1mm、5.5mm、0.1mm、1.2mm和0.4mm。模型对A、B、C级出花率的预测值与实测值之间的R2分别为0.95、0.97、0.96,RMSE分别为0.8%、0.3%、0.9%。本研究建立的模型预测精度较、高参数少,可为日光温室切花郁金香生产中种植期和种植密度的优化提供理论依据和决策支持。     

腹腔镜下输尿管切开取石术疗效探讨

目的探讨腹腔镜下输尿管切开取石术围手术期的护理方法。方法回顾分析88例输尿管结石病人行腹腔镜下切开取石术的术前、术中、术后护理。结果所有患者均得到治愈。88例95侧均取石成功。手术时间平均116min,住院时间平均5．1天,其中1例发生尿漏经治疗后治愈,无腹腔感染发生。结论腹腔镜下输尿管切开取石术是治疗输尿管结石有效、可行的微创技术,通过周密的护理。取得满意效果。     

无机盐对月季切花保鲜效应的研究

含不同无机盐的保鲜剂均能延长月季切花瓶插寿命,增加切花鲜重,增大花径,提高POD活性,改善切花体内水分状况,维持花瓣膜结构的相对稳定。其中以2％蔗糖 300mg／L 8-HQC 200mg／L Ca(N03)2效果最佳。     

Mobile elements and transposition events in the cut locus of Drosophila melanogaster

We have cloned from the Oregon R strain of Drosophila melanogaster a 240 kb segment of DNA that contains the cut (ct) locus, and characterized the region for the presence of repetitive elements. Within this region at least five copies of the suffix element were detected, as well as several putatively novel mobile elements. A number of mutations obtained from the unstable ct ^MR2 strain and its derivatives were mapped within the cut locus. Comparison between parental and daughter strains indicates that frequently two or more independent transposition events involving the cut locus occur simultaneously within a single germ cell, thus providing a molecular basis for the transposition explosion phenomenon.