Physiological variation in metabolic phenotyping and functional genomic studies: use of orthogonal signal correction and PLS-DA

Metabolic phenotyping, or metabotyping, is increasingly being used as a probe in functional genomics studies. However, such profiling is subject to intrinsic physiological variation found in all animal populations. Using a nuclear magnetic resonance-based metabonomic approach, we show that diurnal variations in metabolism can obscure the interpretation of strain-related metabolic differences in two phenotypically normal mouse strains (C57BL10J and Alpk:ApfCD). To overcome this problem, diurnal-related metabolic variation was removed from these spectral data by application of orthogonal signal correction (OSC), a data filtering method. Interpretation of the removed orthogonal variation indicated that diurnal-related variation had been removed and that the AM samples contained higher levels of creatine, hippurate, trimethylamine, succinate, citrate and 2-oxo-glutarate and lower levels of taurine, trimethylamine-N-oxide, spermine and 3-hydroxy-iso-valerate relative to the PM samples. We propose OSC will have great potential removing confounding variation obscuring subtle changes in metabolism in functional genomic studies and will be of benefit to optimising interpretation of proteomic and genomic datasets.     

地形对植被生物量遥感反演的影响——以广州市为例

目前植被生物量遥感反演研究中的地形校正主要是校正地形变化对地表反射率的影响,较少考虑地形起伏引起的像元面积与实际地表面积的差异,而这种差异将导致植被生物量估算结果的偏差.在生物量遥感反演的基础上,结合地表面积计算模型和物质守恒定律,建立了生物量地形校正模型,定量分析和讨论了地形起伏对广州市植被类型面积提取和生物量准确估算的影响.结果表明:地形校正前后全市针叶林、阔叶林、草地、灌木林和园地面积分别增加6.18％、3.70％、2.86％、1.92％和1.29％;在综合分析区域生物量遥感反演中的各种不确定性的基础上,建立的各植被类型的生物量模型均具有较高精度,相关系数均接近或者超过0.9,可以满足生物量反演的要求;全市植被生物量呈现出东、北高,西、南低的分布格局,像元实际代表的林地(阔叶林和针叶林)平均生物量为61.86t/hm2,高于珠三角区域生物量平均值,但与亚热带林的顶级群落生物量水平有较大差距,林地生物量还有较大的增长空间;经过校正地形变化引起的像元面积和实际地表面积差异对生物量提取结果的影响后,植被总生物量比校正前增加了5.82％,5种植被类型的总生物量有不同程度的增加,阔叶林、针叶林、草地、灌木林和园地分别增加了7.74％,4.76％、3.34％、2.50％和1.58％.与其它的表面积计算模型相比,利用的像元地表面积模型具有较高的精度,可以满足生物量遥感估算中地形校正的需要.     

STABILITY IN THE PROPORTION OF HARBOR SEALS HAULED OUT UNDER LOCALLY IDEAL CONDITIONS

We monitored the haul-out behavior of 68 radio-tagged harbor seals ( Phoca vitulina ) during the molt season at two Alaskan haul-out sites (Grand Island, August-September 1994; Nanvak Bay, August-September 2000). For each site, we created a statistical model of the proportion of seals hauled out as a function of date, time of day, tide, and weather covariates. Using these models, we identified the conditions that would result in the greatest proportion of seals hauled out. Although those "ideal conditions" differed between sites, the proportion of seals predicted to be hauled out under those conditions was very similar (81.3% for Grand Island and 85.7% for Nanvak Bay). The similar estimates for both sites suggest that haul-out proportions under locally ideal conditions may be constant between years and geographic regions, at least during the molt season.     

两种生态系统服务价值评估方法比较研究——以四川省金堂县三星镇土地整治工程为例

乡镇土地整治是建设中国美丽乡村的重要途径,对当地生态环境带来正面和负面影响,如何准确评价其生态效益是国家开展土地整治和美丽乡村建设需要面临的重要科学问题。以中国西南部丘陵地区典型乡镇——四川省金堂县三星镇的土地整治工程为例,对比分析了生态系统服务价值当量修正法和单项服务评价法评估土地整治生态效益的异同,以期确定适合我国西南部丘陵地区乡镇土地整治生态效益评估的合理方法。研究结果表明:单项服务评价法的评估结果(生态系统服务价值约300万元)比当量修正法(生态系统服务价值约290万元)高3.5%。当量修正法评估的各项生态系统服务价值增量由高到低依次为:调节服务价值>支持服务价值>供给服务价值>文化服务价值;单项服务评价法评估的生态系统服务价值增量大小排序为:调节服务价值>支持服务价值>文化服务价值>供给服务价值。方法依据和参数的选取不同,导致评估结果具有显著差异,主要表现在单项服务评价法测算的维持养分循环价值、美学景观价值分别是当量修正法的46.90倍和6.94倍,当量修正法测算的水文调节价值是单项服务评价法的5.93倍。单项服务评价法针对各项生态系统服务...     

Bias-reduced estimators of conditional odds ratios in matched case-control studies with unmatched confounding

We study bias-reduced estimators of exponentially transformed parameters in general linear models (GLMs) and show how they can be used to obtain bias-reduced conditional (or unconditional) odds ratios in matched case-control studies. Two options are considered and compared: the explicit approach and the implicit approach. The implicit approach is based on the modified score function where bias-reduced estimates are obtained by using iterative procedures to solve the modified score equations. The explicit approach is shown to be a one-step approximation of this iterative procedure. To apply these approaches for the conditional analysis of matched case-control studies, with potentially unmatched confounding and with several exposures, we utilize the relation between the conditional likelihood and the likelihood of the unconditional logit binomial GLM for matched pairs and Cox partial likelihood for matched sets with appropriately setup data. The properties of the estimators are evaluated by using a large Monte Carlo simulation study and an illustration of a real dataset is shown. Researchers reporting the results on the exponentiated scale should use bias-reduced estimators since otherwise the effects can be under or overestimated, where the magnitude of the bias is especially large in studies with smaller sample sizes.     

Global Positioning System (GPS) location accuracy improvement due to selective availability removal

Global Positioning System (GPS) is an important new technology for spatio-temporal behaviour studies of animals. Differential correction improves location accuracy. Previously, it mostly removed partially the influence of Selective Availability (SA). SA was deactivated in May 2000. The aim of this study was to quantify the influence of SA cancellation on location accuracy of various GPS receivers. We tested the accuracy of locations obtained from non-differential and differential GPS animal collars before and after SA removal. We found a significant improvement in accuracy for both types of GPS collars. However, differential GPS still provides more accurate locations.     

Weighted p-value adjustments for animal carcinogenicity trend test

A typical animal carcinogenicity experiment routinely analyzes approximately 10-30 tumor sites. Comparisons of tumor responses between dosed and control groups and dose-related trend tests are often evaluated for each individual tumor site/type separately. p-Value adjustment approaches have been proposed for controlling the overall Type I error rate or familywise error rate (FWE). However, these adjustments often result in reducing the power to detect a dose effect. This paper proposes using weighted adjustments by assuming that each tumor can be classified as either class A or class B based on prior considerations. The tumors in class A, which are considered as more critical endpoints, are given less adjustment. Two weighted methods of adjustments are presented, the weighted p adjustment and weighted alpha adjustment. A Monte Carlo simulation shows that both weighted adjustments control the FWE well. Furthermore, the power increases if a treatment-dependent tumor is analyzed as in class A tumors and the power decreases if it is analyzed as in class B tumors. A data set from a National Toxicology Program (NTP) 2-year animal carcinogenicity experiment with 13 tumor types/sites observed in male mice was analyzed using the proposed methods. The modified poly-3 test was used to test for increased carcinogenicity since it has been adopted by the NTP as a standard test for a dose-related trend. The unweighted adjustment analysis concluded that there was no statistically significant dose-related trend. Using the Food and Drug Administration classification scheme for the weighted adjustment analyses, two rare tumors (with background rates of 1% or less) were analyzed as class A tumors and 11 common tumors (with background rates higher than 1%) as class B. Both weighted analyses showed a significant dose-related trend for one rare tumor.     

Ab Initio and DFT Study of the Structures,Vibrations and Energetics of the Urea Dimer and Trimer

Stable structures and electronic properties of small urea clusters are investigated with ab initio calculations. We optimized the cluster geometries and calculated the vibrational frequencies with Hartree–Fock (HF), second-order Møller-Plesset perturbation theory (MP2), and Density Functional Theory (DFT) methods using different basis sets. The most stable dimer was found to consist of two nonplanar urea molecules which are connected by two N–-H...O bonds in a common plane, and the most stable trimer has a flat structure of complex and planar C2 form for each urea molecule, like in the crystal. The interaction energies were corrected for the basis set superposition error (BSSE) using the full Boys*ndash;Bernardi counterpoise correction scheme. The stability of different dimer and trimer structures, the features of formation of H-bonds and presented here are compared to the available experimental data.