Modeling the Spatial and Temporal Dependence in fMRI Data

Summary Functional magnetic resonance imaging (fMRI) data sets are large and characterized by complex dependence structures driven by highly sophisticated neurophysiology and aspects of the experimental designs. Typical analyses investigating task‐related changes in measured brain activity use a two‐stage procedure in which the first stage involves subject‐specific models and the second‐stage specifies group (or population) level parameters. Customarily, the first‐level accounts for temporal correlations between the serial scans acquired during one scanning session. Despite accounting for these correlations, fMRI studies often include multiple sessions and temporal dependencies may persist between the corresponding estimates of mean neural activity. Further, spatial correlations between brain activity measurements in different locations are often unaccounted for in statistical modeling and estimation. We propose a two‐stage, spatio‐temporal, autoregressive model that simultaneously accounts for spatial dependencies between voxels within the same anatomical region and for temporal dependencies between a subject's estimates from multiple sessions. We develop an algorithm that leverages the special structure of our covariance model, enabling relatively fast and efficient estimation. Using our proposed method, we analyze fMRI data from a study of inhibitory control in cocaine addicts.     

Unconditional Confidence Interval for the Difference between Two Proportions

In applied statistics it is customary to have to obtain a one‐ or two‐tail confidence interval for the difference d = p₂ – p₁ between two independent binomial proportions. Traditionally, one is looking for a classic and non‐symmetric interval (with respect to zero) of the type d ∈ [δ_L;δ_U], d ≤ δ₀ or d ≥ δ₀. However, in clinical trials, equivalence studies, vaccination efficacy studies, etc., and even after performing the classic homogeneity test, intervals of the type |d| ≤ Δ₀ or |d| ≥ Δ₀, where Δ₀ > 0, may be necessary. In all these cases it is advisable to obtain the interval by inverting the appropriate test. The advantage of this procedure is that the conclusions obtained using the test are compatible with those obtained using the interval. The article shows how this is done using the new exact and asymptotic unconditional tests published. The programs for performing these tests may be obtained at URL http://www.ugr.es/~bioest/software.htm.     

Partial‐Likelihood Analysis of Spatio‐Temporal Point‐Process Data

Summary We investigate the use of a partial likelihood for estimation of the parameters of interest in spatio‐temporal point‐process models. We identify an important distinction between spatially discrete and spatially continuous models. We focus our attention on the spatially continuous case, which has not previously been considered. We use an inhomogeneous Poisson process and an infectious disease process, for which maximum‐likelihood estimation is tractable, to assess the relative efficiency of partial versus full likelihood, and to illustrate the relative ease of implementation of the former. We apply the partial‐likelihood method to a study of the nesting pattern of common terns in the Ebro Delta Natural Park, Spain.     

Genetic Relationships Among Panicle Characteristics of Rice (<Emphasis Type="Italic">Oryza sativa</Emphasis> L.) Using Unconditional and Conditional QTL Analyses

Using mixed-model-based composite interval mapping and conditional statistical methods, we studied quantitative trait loci (QTLs) with epistatic effects and QTLs by environment interaction effects for rice seed set percent (SSP), filled grain number per plant (FGP), and panicle length (PL). A population of 241 recombinant inbred lines was used which was derived from a cross between “Zhenshan 97” and “Minghui 63.” Its linkage map included 221 molecular markers. Our QTL analysis detected 28, 25, and 32 QTLs for SSP, FGP, and PL, respectively. Each QTL explained 1.37%∼13.19% of the mean phenotypic variation. A comparison of conventional and conditional mapping provided information about the genetic control system involved in the synthetic process of SSP, FGP, and PL at the level of individual QTLs. Conditional QTLs with reduced (or increased) effects were identified for SSP, which were significantly influenced by FGP or PL. Some QTLs could express independently for the given traits, thereby providing possibilities for simultaneous improvement of SSR and PL, and SSR and FGP. Epistasis was more sensitive to environmental conditions than were additive effects.     

基于AnyBodyTM技术的人体运动建模方法

人体运动的建模与仿真是当今运动生物力学研究的一个热点.利用数值模型研究人体的运动规律,是人体运动研究的一个重要手段和有效工具.其关键技术在于应用逆向运动学方法求解人体运动,并获取人体运动中各个肌肉力学上技术参数.文中主要探讨基于AnyBodyTM System软件人体运动仿真的建模方法来研究人体运动力学规律,结合The AnyBodyTM system对人体运动具体应用,说明The AnyBodyTM system技术在人体运动仿真领域的优势.     

Conditional Rejection Probabilities of Student's t‐test and Design Adaptations

For clinical trials with interim analyses conditional rejection probabilities play an important role when stochastic curtailment or design adaptations are performed. The conditional rejection probability gives the conditional probability to finally reject the null hypothesis given the interim data. It is computed either under the null or the alternative hypothesis. We investigate the properties of the conditional rejection probability for the one sided, one sample t‐test and show that it can be non monotone in the interim mean of the data and non monotone in the non‐centrality parameter for the alternative. We give several proposals how to implement design adaptations (that are based on the conditional rejection probability) for the t‐test and give a numerical example. Additionally, the conditional rejection probability given the interim t‐statistic is investigated. It does not depend on the unknown σ and can be used in stochastic curtailment procedures. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Spatio-temporal changes in germination and radical elongation of barley seeds tracked by proteome analysis of dissected embryo, aleurone layer, and endosperm tissues

Germination of barley is accompanied by changes in water-soluble seed proteins. 2-DE was used to describe spatio-temporal proteome differences in dissected seed tissues associated with germination and the subsequent radicle elongation. Protein identification by MS enabled assignment of proteins and functions to the seed embryo, aleurone, and endosperm. Abundance in 2-DE patterns was monitored for 48 different proteins appearing in 79 gel spots at 8 time-points up to 72 h post imbibition (PI). In embryo, a beta-type proteasome subunit and a heat shock protein 70 fragment were among the earliest proteins to appear (at 4 h PI). Other early changes were observed that affected spots containing desiccation stress-associated late embryogenesis abundant and abscisic acid (ABA)-induced proteins. From 12 h PI proteins characteristic for desiccation stress disappeared rapidly, as did a putative embryonic protein and an ABA-induced protein, suggesting that these proteins are also involved in desiccation stress. Several redox-related proteins differed in spatio-temporal patterns at the end of germination and onset of radicle elongation. Notably, ascorbate peroxidase that was observed only in the embryo, increased in abundance at 36 h PI. The surprisingly early changes seen in the protein profiles already 4 h after imbibition indicate that germination is programmed during seed maturation.     

Estimation of a Conditional Mean in a Linear Regression Model

Consider the two linear regression models of Y_ij on X_ij, namely Y_ij = β_io + β_il X_ij + ε_ij,j = 1,2,…,n_i, i = 1,2, where ε_ij are assumed to be normally distributed with zero mean and common unknown variance σ². The estimated value of a mean of Y₁ for a given value of X₁ is made to depend on a preliminary test of significance of the hypothesis β₁₁ = β₂₁. The bias and the mean square error of the estimator for the conditional mean of Y₁ are given. The relative efficiency of the estimator to the usual estimator is computed and is used to determine a proper choice of the significance level of the preliminary test.     

Evolution of positive and negative density-dependent dispersal

Understanding the evolution of density-dependent dispersal strategies has been a major challenge for evolutionary ecologists. Some existing models suggest that selection should favour positive and others negative density-dependence in dispersal. Here, we develop a general model that shows how and why selection may shift from positive to negative density-dependence in response to key ecological factors, in particular the temporal stability of the environment. We find that in temporally stable environments, particularly with low dispersal costs and large group sizes, habitat heterogeneity selects for negative density-dependent dispersal, whereas in temporally variable environments, particularly with high dispersal costs and small group sizes, habitat heterogeneity selects for positive density-dependent dispersal. This shift reflects the changing balance between the greater competition for breeding opportunities in more productive patches, versus the greater long-term value of offspring that establish themselves there, the latter being very sensitive to the temporal stability of the environment. In general, dispersal of individuals out of low-density patches is much more sensitive to habitat heterogeneity than is dispersal out of high-density patches.     

酸中毒后室性心律失常仿真研究

本文旨在分析酸中毒对心脏电生理活动的影响,探讨其诱发室性心律失常的机制.首先建立了具有pH和钙/钙调素依赖蛋白激酶Ⅱ(calcium/calmodulin dependent protein kinaseⅡ,Ca MKⅡ)调控作用的人体心室酸中毒计算模型,然后模拟了酸中毒过程中细胞和组织电活动的变化,并定量分析了心电图的改变情况.实验结果表明:在酸中毒期间,细胞动作电位时程的缩短和复极离散度的降低导致心电图QT间期缩短、T波幅值和宽度减小.同时,细胞静息电位的抬高和最大去极化速率的降低也促进了组织电兴奋的缓慢传导和传导阻滞.另外,酸中毒后的初期,肌浆网钙超载促进钙释放增多,导致细胞产生延迟后除极(delayed afterdepolarization,DADs),使心电图上表现为室性早搏.而缓慢传导、传导阻滞和室性早搏有利于折返波的产生,进而发展为室速.因此,酸中毒后细胞的触发活动是诱发室性心律失常的主要原因之一.     

转Bt基因棉花主要抗虫黄酮类化合物时空动态的HPLC分析

棉花植株中的黄酮类化台物是重要的抗病虫害物质。运用高效液相色谱技术,对转Bt基因棉花主要抗虫黄酮类化合物的种类、含量和时空动态进行了初步探讨。结果表明,棉花组织中主要抗虫黄酮类化台物(包括异斛皮苷、芳香苷和槲皮素等)能够用HPLC方法检测并进行定量;异树皮苷、芳香苷和树皮素的含量均以花瓣中最高,花萼、苞叶和棉铃中较少;棉花生长中后期顶端嫩叶中抗虫黄酮类化合物的含量明显高于苗期．不同组织不同生长期的主要抗虫黄酮类化合物含量有一定的差异,所起的抗虫作用也有所不同．     

A Comparison of the Three Conditional Exact Tests in Two‐way Contingency Tables Using the Unconditional Exact Power

The conditional exact tests of homogeneity of two binomial proportions are often used in small samples, because the exact tests guarantee to keep the size under the nominal level. The Fisher's exact test, the exact chi‐squared test and the exact likelihood ratio test are popular and can be implemented in software StatXact. In this paper we investigate which test is the best in small samples in terms of the unconditional exact power. In equal sample cases it is proved that the three tests produce the same unconditional exact power. A symmetry of the unconditional exact power is also found. In unequal sample cases the unconditional exact powers of the three tests are computed and compared. In most cases the Fisher's exact test turns out to be best, but we characterize some cases in which the exact likelihood ratio test has the highest unconditional exact power. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Coarse-grained Modeling and Simulation of Actin Filament Behavior Based on Brownian Dynamics Method

The actin filament, which is the most abundant component of the cytoskeleton, plays important roles in fundamental cellular activities such as shape determination, cell motility, and mechanosensing. In each activity, the actin filament dynamically changes its structure by polymerization, depolymerization, and severing. These phenomena occur on the scales ranging from the dynamics of actin molecules to filament structural changes with its deformation due to the various forces, for example, by the membrane and solvent. To better understand the actin filament dynamics, it is important to focus on these scales and develop its mathematical model. Thus, the objectives of this study were to model and simulate actin filament polymerization, depolymerization, and severing based on the Brownian dynamics method. In the model, the actin monomers and the solvent were considered as globular particles and a continuum, respectively. The motion of the actin molecules was assumed to follow the Langevin equation. The polymerization, which increases the filament length, was determined by the distance between the center of the actin particle at the barbed end and actin particles in the solvent. The depolymerization, which decreases the filament length, was modeled such that the number of dissociation particles from the filament end per unit time was constant. In addition, the filament severing, in which one filament divides into two, was modeled to occur at an equal rate along the filament. Then, we simulated the actin filament dynamics using the developed model, and analyzed the filament elongation rate, its turnover, and the effects of filament severing on the polymerization and depolymerization. Results indicated that the model reproduced the linear dependence of the filament elongation on time, filament turnover process by polymerization and depolymerization, and acceleration of the polymerization and depolymerization by severing, which qualitatively agreed with those observed in experiments.     

Conditional dispersal, clines, and the evolution of dispersiveness

Conditional dispersal, in which an individual’s decision over whether to disperse is a response to environmental conditions, features prominently in studies of dispersal evolution. Using models of clines, I examine how one widely discussed cost of dispersal, namely, that dispersal impedes local adaptation, changes with conditional dispersal and what this implies for dispersal evolution. I examine the consequences for dispersal evolution of the responsiveness of dispersal to the environment, the accuracy of any proximal cues that individuals rely upon to assess habitat quality, and whether dispersal responds to fitness itself or only to some fitness components (juvenile survivorship). All of the conditional dispersal behaviors that I consider weaken the indirect cost of dispersal inhibiting local adaptation. However, if individuals rely on imprecise cues to assess habitat quality and base dispersal decisions on juvenile survivorship, then conditional dispersal can incur additional costs by exacerbating overcrowding. Conditional dispersal initially leads to steeper clines in traits under direct selection, but when dispersiveness can itself evolve, conditional dispersal allows sigmoidal clines to persist long after those obtained with unconditional movement would become stepped. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Modeling and Simulation of Flow Batteries

Flow batteries have received extensive recognition for large‐scale energy storage such as connection to the electricity grid, due to their intriguing features and advantages including their simple structure and principles, long operation life, fast response, and inbuilt safety. Market penetration of this technology, however, is still hindered by some critical issues such as electroactive species crossover and its corresponding capacity loss, undesirable side reactions, scale‐up and optimization of structural geometries at different scales, and battery operating conditions. Overcoming these remaining challenges requires a comprehensive understanding of the interrelated structural design parameters and the multivariable operations within the battery system. Numerical modeling and simulation are effective tools not only for gaining an understanding of the underlying mechanisms at different spatial and time scales of flow batteries but also for cost‐effective optimization of reaction interfaces, battery components, and the entire system. Here, the research and development progress in modeling and simulation of flow batteries is presented. In addition to the most studied all‐vanadium redox flow batteries, the modelling and simulation efforts made for other types of flow battery are also discussed. Finally, perspectives for future directions on model development for flow batteries, particularly for the ones with limited model‐based studies are highlighted.     

籼稻稻米蛋白质含量与外观品质性状间不同遗传体系的条件遗传相关分析

选用稻米蛋白质含量等品质差异较大的7个籼型不育系(A)及相应的保持系(B)与5个籼型恢复系(R)杂交,组成7×5不完全双列杂交组合。应用包括胚乳、细胞质和母体植株基因的遗传主效应以及基因型×环境互作效应的数量性状遗传模型及非条件和条件分析方法,研究了籼稻稻米蛋白质含量与外观品质性状间的遗传相关性,进一步揭示了籼稻糙米重、稻米直链淀粉含量对稻米蛋白质含量与外观品质性状间遗传相关性的影响。非条件分析的结果表明,除了与糙米厚的相关性未达到显著水平以外,蛋白质含量与其它稻米外观品质性状间的遗传相关性均达极显著水平,其中与糙米宽间的相关性表现为正值,其余为负向相关。条件分析的结果显示,糙米重和直链淀粉含量对稻米蛋白质含量与外观品质性状间的遗传相关性均可产生较大的影响。糙米重主要通过基因型×环境互作效应影响蛋白质含量与外观品质性状间的遗传相关性,其中对蛋白质含量与糙米长、糙米宽、糙米厚间遗传相关性的影响主要表现为负向作用,而对蛋白质含量与糙米长宽比、糙米长厚比间遗传相关性的影响则表现为正向作用。稻米直链淀粉主要通过细胞质遗传主效应和母体加性效应影响蛋白质含量与糙米长、糙米长宽比、糙米长厚比间的遗传相关性,而对蛋白质含量与糙米宽间的相关性影响主要表现为负向作用。     

工业生物发酵过程模拟：进展与发展趋势

工业生物发酵是工业生物技术规模化生产必需的基本操作单元。对微生物细胞及其反应器进行数学模拟将有助于加深对发酵过程的理解,也将为新的合成生物构建提供解决策略。文中对工业发酵系统的特点、数学模拟的发展历史、数学模型的分类和特点、用途等作了深入阐述,并展望了全发酵系统模拟的发展趋势。