Uncoordinated Muscular Response to Microsecond Electrical Pulses Is a Manifestation of Simultaneous Multiple Spinal Reflexes

This article has no abstract.     

Time Varying Optimization for Monitoring Multiple Contaminants under Uncertain Hydrogeology

This study presents a method for identifying cost effective sampling designs for long-term monitoring of remediation of groundwater over multiple monitoring periods under uncertain flow conditions. A contaminant transport model is used to simulate plume migration under many equally likely stochastic hydraulic conductivity fields and provides representative samples of contaminant concentrations. Monitoring costs are minimized under a constraint to meet an acceptable level of error in the estimation of total mass for multiple contaminants simultaneously over many equiprobable realizations of hydraulic conductivity field. A new myopic heuristic algorithm (MS-ER) that combines a new error-reducing search neighborhood is developed to solve the optimization problem. A simulated annealing algorithm using the error-reducing neighborhood (SA-ER) and a genetic algorithm (GA) are also considered for solving the optimization problem. The method is applied to a hypothetical aquifer where enhanced anaerobic bioremediation of four toxic chlorinated ethene species is modeled using a complex contaminant transport model. The MS-ER algorithm consistently performed better in multiple trials of each algorithm when compared to SA-ER and GA. The best design of MS-ER algorithm produced a savings of nearly 25% in project cost over a conservative sampling plan that uses all possible locations and samples.     

Time Varying Optimization for Monitoring Multiple Contaminants under Uncertain Hydrogeology

This study presents a method for identifying cost effective sampling designs for long-term monitoring of remediation of groundwater over multiple monitoring periods under uncertain flow conditions. A contaminant transport model is used to simulate plume migration under many equally likely stochastic hydraulic conductivity fields and provides representative samples of contaminant concentrations. Monitoring costs are minimized under a constraint to meet an acceptable level of error in the estimation of total mass for multiple contaminants simultaneously over many equiprobable realizations of hydraulic conductivity field. A new myopic heuristic algorithm (MS-ER) that combines a new error-reducing search neighborhood is developed to solve the optimization problem. A simulated annealing algorithm using the error-reducing neighborhood (SA-ER) and a genetic algorithm (GA) are also considered for solving the optimization problem. The method is applied to a hypothetical aquifer where enhanced anaerobic bioremediation of four toxic chlorinated ethene species is modeled using a complex contaminant transport model. The MS-ER algorithm consistently performed better in multiple trials of each algorithm when compared to SA-ER and GA. The best design of MS-ER algorithm produced a savings of nearly 25% in project cost over a conservative sampling plan that uses all possible locations and samples.     

Landscape Ecotoxicology and Assessment of Risk at Multiple Scales

Traditional approaches to ecotoxicology and ecological risk assessment frequently have ignored the complexities arising due to the spatial heterogeneity of natural systems. In recent years, however, ecologists have become increasingly aware of the influence of spatial organization on ecological processes. Landscape ecology provides a conceptual and theoretical framework for the analysis of spatial patterns, the characterization of spatial aspects of ecosystem function, and the understanding of landscape dynamics. Incorporating the insights of landscape ecology into ecotoxicology will enhance our ability to understand and ultimately predict the effects of toxic substances in ecological systems. Ecological risk assessments need to explicitly consider multiple spatial scales, accounting for heterogeneity within contaminated areas and for the larger landscape context. A simple simulation model is presented to illustrate the effects of spatial heterogeneity by linking an individual-based toxicokinetic model with a spatially distributed metapopulation model. Dispersal of organisms between contaminated and uncontaminated patches creates a situation where risk analysis must consider a spatial extent broader than the toxicant-contaminated area. In general, the addition of a toxicant to a source patch (i.e., a net exporter of individuals) will have a greater impact than the same toxicant addition to a sink patch (i.e., a net importer of individuals).     

城市高架桥的景观优化途径初探

21世纪以来,中国进入快速城市化进程。市政基础设施之一的城市高架桥作为现代城市演进的必然产物,成为城市景观的重要组成部分,但其在解决城市交通问题的同时,也带来一系列诸如环境污染、景观破坏等城市问题。本文将城市高架桥在景观语境下进行剖析,从高架桥自身形态美化、废弃高架桥的景观利用与再生、拆除高架桥后的生态修复3个方面,结合国内外成功的实践案例,提出了城市高架桥的景观优化途径,并倡导在中国推行城市市政基础设施景观化的基本理念。     

A Hierarchical Regulatory Landscape during the Multiple Stages of EMT

1. Download high-res image (355KB)
2. Download full-size image

     

Free Energy Landscape and Multiple Folding Pathways of an H-Type RNA Pseudoknot

How RNA sequences fold to specific tertiary structures is one of the key problems for understanding their dynamics and functions. Here, we study the folding process of an H-type RNA pseudoknot by performing a large-scale all-atom MD simulation and bias-exchange metadynamics. The folding free energy landscapes are obtained and several folding intermediates are identified. It is suggested that the folding occurs via multiple mechanisms, including a step-wise mechanism starting either from the first helix or the second, and a cooperative mechanism with both helices forming simultaneously. Despite of the multiple mechanism nature, the ensemble folding kinetics estimated from a Markov state model is single-exponential. It is also found that the correlation between folding and binding of metal ions is significant, and the bound ions mediate long-range interactions in the intermediate structures. Non-native interactions are found to be dominant in the unfolded state and also present in some intermediates, possibly hinder the folding process of the RNA.     

Landscape Management of Fire and Grazing Regimes Alters the Fine-Scale Habitat Utilisation by Feral Cats

Intensification of fires and grazing by large herbivores has caused population declines in small vertebrates in many ecosystems worldwide. Impacts are rarely direct, and usually appear driven via indirect pathways, such as changes to predator-prey dynamics. Fire events and grazing may improve habitat and/or hunting success for the predators of small mammals, however, such impacts have not been documented. To test for such an interaction, we investigated fine-scale habitat selection by feral cats in relation to fire, grazing and small-mammal abundance. Our study was conducted in north-western Australia, where small mammal populations are sensitive to changes in fire and grazing management. We deployed GPS collars on 32 cats in landscapes with contrasting fire and grazing treatments. Fine-scale habitat selection was determined using discrete choice modelling of cat movements. We found that cats selected areas with open grass cover, including heavily-grazed areas. They strongly selected for areas recently burnt by intense fires, but only in habitats that typically support high abundance of small mammals. Intense fires and grazing by introduced herbivores created conditions that are favoured by cats, probably because their hunting success is improved. This mechanism could explain why, in northern Australia, impacts of feral cats on small mammals might have increased. Our results suggest the impact of feral cats could be reduced in most ecosystems by maximising grass cover, minimising the incidence of intense fires, and reducing grazing by large herbivores.     

自由就诊模式下预约诊疗服务管理研究

通过文件资料回顾和上海市案例研究,了解在自由就诊模式下开展预约诊疗服务工作存在的问题与挑战,集中体现在预约诊疗服务平台的发展缺乏可持续性,预约内容和途径的拓展受到现实因素的制约,“实名制预约”和“预约优先”的落实面临挑战,当前预约诊疗服务工作自身也存在局限性。建议通过拓展预约方式、建立费用约束机制和利用服务规则来强化预约诊疗服务管理,同时积极开展公众宣传教育和发挥改革举措之间的协同作用。

     

The Landscape of the Prion Protein's Structural Response to Mutation Revealed by Principal Component Analysis of Multiple NMR Ensembles

Prion Proteins (PrP) are among a small number of proteins for which large numbers of NMR ensembles have been resolved for sequence mutants and diverse species. Here, we perform a comprehensive principle components analysis (PCA) on the tertiary structures of PrP globular proteins to discern PrP subdomains that exhibit conformational change in response to point mutations and clade-specific evolutionary sequence mutation trends. This is to our knowledge the first such large-scale analysis of multiple NMR ensembles of protein structures, and the first study of its kind for PrPs. We conducted PCA on human (n = 11), mouse (n = 14), and wildtype (n = 21) sets of PrP globular structures, from which we identified five conformationally variable subdomains within PrP. PCA shows that different non-local patterns and rankings of variable subdomains arise for different pathogenic mutants. These subdomains may thus be key areas for initiating PrP conversion during disease. Furthermore, we have observed the conformational clustering of divergent TSE-non-susceptible species pairs; these non-phylogenetic clusterings indicate structural solutions towards TSE resistance that do not necessarily coincide with evolutionary divergence. We discuss the novelty of our approach and the importance of PrP subdomains in structural conversion during disease.     

医院质量监测系统在医院管理及临床服务中的应用

医院质量监测系统（HQMS）作为医疗服务监管信息网络直报平台,对建立全国性医疗服务质量与效率资料库,提供医院评审评价数据支持,促进医院内部持续改进具有重要作用。文章将医院应用HQMS进行医疗质量管理和持续改进的具体实践以及取得的成效进行了总结,可以为各医院医疗质量管理提供有益参考。     

The Population Genetics of Adaptation: Multiple Substitutions on a Smooth Fitness Landscape

Much recent work in the theoretical study of adaptation has focused on the so-called strong selection–weak mutation (SSWM) limit, wherein adaptation is due to new mutations of definite selective advantage. This work, in turn, has focused on the first step (substitution) during adaptive evolution. Here we extend this theory to allow multiple steps during adaptation. We find analytic solutions to the probability that adaptation follows a certain path during evolution as well as the probability that adaptation arrives at a given genotype regardless of the path taken. We also consider the probability of parallel adaptation and the proportion of the total increase in fitness caused by the first substitution. Our key assumption is that there is no epistasis among beneficial mutations.RECENTLY, there has been a great deal of interest in the genetics of adaptation. While much of this interest has focused on experimental studies of adaptive evolution (e.g., Lenski and Travisano 1994; Holder and Bull 2001; Rokyta et al. 2005; Weinreich et al. 2006; Betancourt 2009), there has also been considerable interest in theoretical analyses of adaptation (reviewed in Gillespie 1991; Orr 2005; Joyce et al. 2008), a topic that was, until recently, surprisingly neglected.These theoretical studies have considered a number of questions: What does the distribution of fitness effects among new beneficial mutations look like? What does the distribution of fitness effects among fixed beneficial mutations look like? How does clonal interference among competing mutations distort this distribution? Do early substitutions generally have larger effects on fitness than later ones? And how likely is it that independently evolving populations substitute the same beneficial mutations?A number of approaches have been taken to these and similar questions, including analysis of phenotypic and DNA sequence-based models. Among sequence-based studies, a good deal of attention has focused on the so-called strong selection–weak mutation (SSWM) scenario, introduced by Gillespie (1983, 1984, 1991). Under this scenario, selection is strong enough that mutations are either definitely beneficial or definitely deleterious and neutral mutations are not allowed. Also, mutation is weak enough that the population is, at any point in time, essentially composed of a single wild-type DNA sequence and mutations are rare enough that double mutants and the complications of clonal interference (Gerrish and Lenski 1998) can be ignored. Adaptation in the SSWM domain thus involves the appearance and substitution of new mutations. It is usually assumed that adaptation occurs in response to a sudden change in the environment. Recurrent mutation from the current (and now somewhat maladapted) wild-type allele produces different beneficial mutations. While most of these new mutations are lost accidentally by genetic drift each time they appear, one mutation will ultimately escape stochastic loss and be substituted. At this point, the population arrives at a new wild-type sequence and the process begins anew. Adaptation thus features the stepwise substitution of single mutations.Even in this simple SSWM scenario, mathematical analysis of adaptation has proved difficult. The most important results were derived by Gillespie (1983, 1984, 1991) himself. Given recurrent mutation from a wild-type DNA sequence to m different beneficial mutations, Gillespie calculated the probability that natural selection would, at the next substitution event, fix any particular one of these mutations. His result, as explained in more detail below, revealed that the probability that a particular mutation is fixed at the next event depends on the magnitude of its selective advantage relative to those of all available beneficial mutations. Gillespie was thus able to write down transition probabilities for the next substitution event in adaptation. As empirical studies of adaptation accumulate, it is of interest to examine the predictability of those patterns observed when populations adapt via multiple substitutions.Here we extend Gillespie''s analysis to allow multiple substitution events. Specifically, we show how one can calculate the probability that a population will, after the substitution of several beneficial mutations, arrive at a particular genotype. We also calculate the probability that evolution takes a particular path to this genotype, as well as the probability that two independently evolving populations adapt in parallel, arriving at the same genotype after multiple substitutions. One of our results was derived previously by Weinreich et al. (2006). For completeness and clarity we briefly rederive his result here. As expected, we find that Gillespie''s one-substitution results become special cases of our multiple-substitution results.As emphasized below, our key assumption is that the beneficial effects of mutations are independent; i.e., no epistasis occurs among mutations. As we also emphasize, our analysis proves more difficult mathematically than Gillespie''s because the study of multiple substitutions given independent fitness effects necessarily involves a complex dependence on history: the identity of mutations fixed late during adaptation depends on the identity of mutations fixed earlier.     

多元肥料效应函数模型的优化方法

本文对多元肥料效应函数模型的优化问题进行了分析,根据数学规划理论建立了对多元肥料效应函数进行优化的数学模型,给出了具体的计算方法。该方法经实践检验,效果很好。     

Rapid Assessment of Ecosystem Services Provided by Two Mineral Extraction Sites Restored for Nature Conservation in an Agricultural Landscape in Eastern England

Despite growing recognition that mineral sites restored for nature conservation can enhance local biodiversity, the wider societal benefits provided by this type of restoration relative to alternative options are not well understood. This study addresses this research gap by quantifying differences in ecosystem services provision under two common mineral site after-uses: nature conservation and agriculture. Using a combination of site-specific primary field data, benefits transfer and modelling, we show that for our sites restoration for nature conservation provides a more diverse array of ecosystem services than would be delivered under an agricultural restoration scenario. We also explore the effects of addressing different conservation targets, which we find alter the provision of ecosystem services on a service-specific basis. Highly species-focused intervention areas are associated with increased carbon storage and livestock grazing provision, whereas non-intervention areas are important for carbon sequestration, fishing, recreation and flood risk mitigation. The results of this study highlight the wider societal importance of restored mineral sites and may help conservation managers and planners to develop future restoration strategies that provide benefits for both biodiversity and human well-being.     

日本地域景观的独特性及其可持续管理

日本国土面积虽小,却具备多样的地形条件和气候类型。经过长期磨合,日本各地人与自然的关系不尽相同,因此每个地域的景观也各具特色。从日本全国范围来看,景观的类型十分丰富。21 世纪之后,日本法律体系的调整强调了地域景观独特性的重要性,并将景观看作地域规划中的重要资源。为了适应这种景观价值观的变化,日本开始建立新的景观管理规划理论,并为景观管理提供新的思路和方法论,包括新的财务资源、执行组织等。根据这一趋势,风景园林师的职责和所需具备的素质能力也发生了改变。今后,风景园林设计师不仅需要能够创造新的景观（即景观设计）,而且需要具备读取当地景观独特性（即风景解读）的能力。     

The Level and Landscape of Optimization in the Origin of the Genetic Code

We consider a model of the origin of genetic code organization incorporating the biosynthetic relationships between amino acids and their physicochemical properties. We study the behavior of the genetic code in the set of codes subject both to biosynthetic constraints and to the constraint that the biosynthetic classes of amino acids must occupy only their own codon domain, as observed in the genetic code. Therefore, this set contains the smallest number of elements ever analyzed in similar studies. Under these conditions and if, as predicted by physicochemical postulates, the amino acid properties played a fundamental role in genetic code organization, it can be expected that the code must display an extremely high level of optimization. This prediction is not supported by our analysis, which indicates, for instance, a minimization percentage of only 80%. These observations can therefore be more easily explained by the coevolution theory of genetic code origin, which postulates a role that is important but not fundamental for the amino acid properties in the structuring of the code. We have also investigated the shape of the optimization landscape that might have arisen during genetic code origin. Here, too, the results seem to favor the coevolution theory because, for instance, the fact that only a few amino acid exchanges would have been sufficient to transform the genetic code (which is not a local minimum) into a much better optimized code, and that such exchanges did not actually take place, seems to suggest that, for instance, the reduction of translation errors was not the main adaptive theme structuring the genetic code.