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Abstract action potential models for toxin recognition 摘要:毒素识别的动作电位模型
Pub Date : 2005-12-01 DOI: 10.1080/10273660500533898
J. Peterson, T. Khan
In this paper, we present a robust methodology using mathematical pattern recognition schemes to detect and classify events in action potentials for recognizing toxins in biological cells. We focus on event detection in action potential via abstraction of information content into a low dimensional feature vector within the constrained computational environment of a biosensor. We use generated families of action potentials from a classic Hodgkin–Huxley model to verify our methodology and build toxin recognition engines. We demonstrate that good recognition rates are achievable with our methodology.
在本文中,我们提出了一种强大的方法,使用数学模式识别方案来检测和分类识别生物细胞中毒素的动作电位事件。我们专注于通过将信息内容抽象为生物传感器有限计算环境中的低维特征向量来检测动作电位中的事件。我们使用从经典霍奇金-赫胥黎模型生成的动作电位族来验证我们的方法并构建毒素识别引擎。我们证明,使用我们的方法可以实现良好的识别率。
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引用次数: 1
A numerical investigation of heat transfer cardiac output measurements 热传递心输出量测量的数值研究
Pub Date : 2005-09-01 DOI: 10.1080/10273660500158712
P. Fotheringham, A. Gourlay, S. McKee, S. Andrews
Measurement of cardiac output is often investigated using a technique based on hot-film anemometry. Here, we discuss a modification to hot-film anemometry, which involves a cylindrical heating element mounted flush on the surface of a typical Swan-Ganz catheter. In contrast to traditional thermodilution, the method discussed here has the potential to allow continuous monitoring of cardiac output. This paper demonstrates that there is a simple approximate relationship between the power input to the device to maintain a temperature of one degree above blood heat and cardiac output. Since, the heat transfer and the fluid flow decouple, a numerical model of the heat transfer of a cylindrical catheter (with heating element) sitting concentrically within a rigid cylindrical artery is developed. Numerical results were obtained for a wide selection of flow profiles, including experimental data. The results indicate that the cardiac output/power input relationship is extremely robust with respect to flow profile and system parameter variation.
心输出量的测量通常使用基于热膜风速测量的技术进行研究。在这里,我们讨论了一种改进的热膜风速计,它涉及一个圆柱形加热元件安装在一个典型的Swan-Ganz导管的表面上。与传统的热稀释相比,本文讨论的方法具有允许连续监测心输出量的潜力。本文证明,在设备的功率输入之间有一个简单的近似关系,以保持温度高于血热一度的心脏输出量。由于传热与流体流动不耦合,建立了圆柱形导管(带加热元件)同心放置于刚性圆柱形动脉内的传热数值模型。数值结果得到了广泛的选择流型,包括实验数据。结果表明,心输出量/功率输入关系在流量分布和系统参数变化方面是非常稳健的。
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引用次数: 2
A coarse grained model for DNA and polymer packaging: statics and dynamics DNA和聚合物包装的粗粒度模型:静力学和动力学
Pub Date : 2005-06-01 DOI: 10.1080/10273660500149927
I. Ali, D. Marenduzzo, C. Micheletti, J. Yeomans
We present a numerical characterization of the statics and dynamics of the packaging of a semi-flexible polymer inside a sphere. The study is motivated by recent experiments on the packaging of DNA inside viral capsids. It is found that the force required to confine the coarse-grained polymer is in fair agreement with that found in experiments for the packaging of the phi29 bacteriophage genome. Despite its schematic nature, the model is capable of reproducing the most salient dynamical features of packaging experiments such as the presence of pauses during individual packaging processes and the trend of the resisting force as a function of chain packed fraction.
我们提出了半柔性聚合物在球内封装的静力学和动力学的数值表征。这项研究的动机是最近对病毒衣壳内DNA包装的实验。研究发现,限制粗粒聚合物所需的力与phi29噬菌体基因组包装实验中发现的力相当一致。尽管它是示意图性质,但该模型能够再现包装实验中最显著的动态特征,例如在单个包装过程中存在停顿,以及阻力作为链包装分数的函数的趋势。
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引用次数: 3
Flexibility and assembly of viral capsids 病毒衣壳的灵活性和组装
Pub Date : 2005-06-01 DOI: 10.1080/10273660500148804
M. Thorpe
We present a novel approach to the calculation of flexibility and mobility in proteins, protein complexes and other large macromolecular complexes like virus capsids. Rather than using conventional molecular dynamics, we use the constraint approach of Lagrange, incorporating covalent bonds, hydrogen bonds and tethers for hydrophobic interactions. The rigid clusters, including the core, as well as the flexible joints between them are identified. Subsequently, this can be used as the basis for dynamics, using Monte Carlo approaches that maintain all the original constraints, as well as van der Waals excluded volumes. In our original work [1,2], we focused on ring closure and added the side groups later. This was successful in exploring the available conformational space and also in exploring directed trajectories between known distinct protein structures. We show that such techniques can be used on a single X-ray crystallographic structure to generate an ensemble of structures remarkably similar to those observed in NMR [2]. We also show how this approach can be used to generate multiple protein complexes for use in ligand docking studies, as well as exploring the allowed conformations of protein‐ligand complexes. This approach, applied at the atomic level, can handle macromolecular assemblies of up to a million atoms, to determine the rigid regions and the flexible joints between them. An application of this approach to the stability and assembly of an icosahedral viral capsid and cowpea chlorotic mottle virus are discussed [3].
我们提出了一种新的方法来计算蛋白质、蛋白质复合物和其他大型大分子复合物(如病毒衣壳)的柔韧性和流动性。而不是使用传统的分子动力学,我们使用拉格朗日的约束方法,结合共价键,氢键和系绳的疏水相互作用。确定了刚性集群,包括核心,以及它们之间的柔性关节。随后,这可以用作动力学的基础,使用蒙特卡罗方法保持所有原始约束,以及范德华排除的体积。在我们最初的工作[1,2]中,我们主要关注环闭包,并在之后添加了侧群。这在探索可用的构象空间和探索已知不同蛋白质结构之间的定向轨迹方面是成功的。我们表明,这种技术可以用于单个x射线晶体学结构,以产生与NMR[2]中观察到的结构非常相似的结构系综。我们还展示了如何使用这种方法生成用于配体对接研究的多种蛋白质复合物,以及探索蛋白质-配体复合物的允许构象。这种方法应用于原子水平,可以处理多达一百万个原子的大分子组件,以确定它们之间的刚性区域和柔性关节。本文讨论了该方法在二十面体病毒衣壳的稳定性和组装以及豇豆绿斑病毒中的应用。
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引用次数: 0
Lattice Transformations and Subunit Conformational Changes in Phage Capsid Maturation 噬菌体衣壳成熟过程中的晶格转化和亚基构象变化
Pub Date : 2005-06-01 DOI: 10.1080/10273660500149646
D. Gossard, J. King
A general feature of the pathways for the assembly of double-stranded DNA phages and viruses is the assembly of coat and scaffolding subunits into a precursor shell or procapsid, followed by packaging of the genomic DNA into the shell. Coupled to this DNA packaging process is the loss of the scaffolding subunits and expansion and re-organization of the procapsid lattice to the lattice of the mature virus. Such lattice transitions have also been observed with adenoviruses and herpesviruses. In re-organizing into the mature capsid lattice, each subunit of the precursor lattice must change its conformation, or its relationship with its neighbours, or both. We briefly review here recent structural data for phages P22 and HK97, and describe the motions and conformational changes associated with this lattice transition. Possible functions of such constrained transformations within the virus life-cycle are discussed.
双链DNA噬菌体和病毒组装途径的一个一般特征是将外壳和支架亚基组装成前体壳或原壳,然后将基因组DNA包装到壳中。与这一DNA包装过程相耦合的是脚手架亚基的丢失以及原衣壳晶格向成熟病毒晶格的扩展和重组。在腺病毒和疱疹病毒中也观察到这种晶格转变。在重组成成熟衣壳晶格的过程中,前体晶格的每个亚基必须改变其构象,或与其相邻的关系,或两者兼而有之。我们简要回顾了噬菌体P22和HK97的最新结构数据,并描述了与这种晶格转变相关的运动和构象变化。讨论了病毒生命周期内这种约束转换的可能函数。
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引用次数: 1
Dissecting the fine details of assembly of a T=3 phage capsid 剖析T=3噬菌体衣壳组装的细节
Pub Date : 2005-06-01 DOI: 10.1080/10273660500149869
P. Stockley, A. Ashcroft, S. Francese, G. Thompson, N. Ranson, A. Smith, S. Homans, N. Stonehouse
The RNA bacteriophages represent ideal model systems in which to probe the detailed assembly pathway for the formation of a T = 3 quasi-equivalent capsid. For MS2, the assembly reaction can be probed in vitro using acid disassembled coat protein subunits and a short (19 nt) RNA stem-loop that acts as the translational operator of the replicase gene and leads to sequence-specific sequestration and packaging of the cognate phage RNA in vivo. Reassembly reactions can be initiated by mixing these components at neutral pH. The molecular basis of the sequence-specific RNA–protein interaction is now well understood. Recent NMR studies on the protein demonstrate extensive mobility in the loops of the polypeptide that alter their conformations to form the quasi-equivalent conformers of the final capsid. It seems reasonable to assume that RNA binding results in reduction of this flexibility. However, mass spectrometry suggests that these RNA–protein complexes may only provide one type of quasi-equivalent capsid bui...
RNA噬菌体代表了理想的模型系统,在其中探索T = 3准等效衣壳形成的详细组装途径。对于MS2,可以利用酸分解的外壳蛋白亚基和短(19 nt)的RNA茎环在体外探测组装反应,该茎环作为复制酶基因的翻译操作符,在体内导致同源噬菌体RNA的序列特异性隔离和包装。重组反应可以通过在中性ph下混合这些组分来启动。序列特异性rna -蛋白相互作用的分子基础现在已经很好地理解了。最近对蛋白质的核磁共振研究表明,多肽的环具有广泛的流动性,改变了它们的构象,形成了最终衣壳的准等效构象。假设RNA结合导致这种灵活性的降低似乎是合理的。然而,质谱分析表明,这些rna -蛋白复合物可能只提供一种准等效衣壳结构。
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引用次数: 11
Spatial correlation of gene expression measures in tissue microarray core analysis 组织芯片核心分析中基因表达测量的空间相关性
Pub Date : 2005-03-01 DOI: 10.1080/10273660500035795
M. Emily, D. Morel, R. Marcelpoil, O. François
Tissue microarrays (TMAs) make possible the screening of hundreds of different tumour samples for the expression of a specific protein. Automatic features extraction procedures lead to a series of covariates corresponding to the averaged stained scores. In this article, we model the random geometry of TMA cores using voronoi tesselations. This formalism enables the computation of indices of spatial correlation of stained scores using both classical and novel approaches. The potential of these spatial statistics to correctly discriminate between diseased and non-diseased cases is evaluated through the analysis of a TMA containing samples of breast carcinoma data. The results indicate a significant improvement in the breast cancer prognosis.
组织微阵列(TMAs)使筛选数百种不同的肿瘤样本以表达特定蛋白质成为可能。自动特征提取程序会产生一系列对应于平均染色分数的协变量。在本文中,我们使用voronoi镶嵌来模拟TMA岩心的随机几何形状。这种形式可以使用经典和新颖的方法计算染色分数的空间相关性指数。通过对包含乳腺癌数据样本的TMA分析,评估了这些空间统计正确区分患病和非患病病例的潜力。结果表明乳腺癌预后有显著改善。
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引用次数: 9
Bone formation: Biological aspects and modelling problems 骨形成:生物学方面和建模问题
Pub Date : 2005-03-01 DOI: 10.1080/10273660412331336883
M. A. Herrero, José M. López
In this work we succintly review the main features of bone formation in vertebrates. Out of the many aspects of this exceedingly complex process, some particular stages are selected for which mathematical modelling appears as both feasible and desirable. In this way, a number of open questions are formulated whose study seems to require interaction among mathematical analysis and biological experimentation.
在这项工作中,我们简要回顾了脊椎动物骨形成的主要特征。在这个极其复杂的过程的许多方面中,选择了一些特定的阶段,数学建模似乎既可行又可取。通过这种方式,形成了许多开放性问题,这些问题的研究似乎需要数学分析和生物实验之间的相互作用。
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引用次数: 15
Could Condoms Stop the AIDS Epidemic 避孕套能阻止艾滋病的流行吗
Pub Date : 2003-09-01 DOI: 10.1080/10273660412331315147
S. Moghadas, A. Gumel, Robert G. McLeod, R. Gordon
Although therapeutic treatment strategies appear promising for retarding the progression of HIV-related diseases, prevention remains the most effective strategy against the HIV/AIDS epidemic. This paper focuses on the effect of condom use as a single-strategy approach in HIV prevention in the absence of any treatment. There are two primary factors in the use of condoms to halt the HIV/AIDS epidemic: condom efficacy and compliance. Our study is focused on the effect of these factors in stopping the epidemic by constructing a new deterministic mathematical model. The current estimate of condom effectiveness against HIV transmission, based on the latest meta-analysis, is 60–96%, with a mean of 87%. Since the parameter estimates are subject to different kinds of uncertainty, to achieve adequate quality assurance in predictions, uncertainty and sensitivity analyses are carried out using latin hypercube sampling (LHS) and partial rank correlation coefficients (PRCCs). Using stability and sensitivity analyses, based on a plausible range of parameter values, key parameters that govern the persistence or eradication of HIV are identified. This analysis shows that the product of efficacy and compliance, which we call ‘preventability’ (p), has a negative effect on the epidemic; as increasing p decreases the level of epidemicity. It is also shown that the threshold preventability (pc) increases with increasing average number of HIV-infected partners of susceptible individuals, especially those in the AIDS stage. For populations where the average number of HIV-infected partners is large, the associated preventability threshold is high and perhaps unattainable, suggesting that for such a population, HIV may not be controlled using condoms alone. On the other hand, for a population where the average number of HIV-infected partners is low (within a reasonable range), it is shown that pc is about 75%, suggesting that the epidemic could be stopped using condoms. Thus, for such a population, public health measures that can bring preventability above the threshold and continuous quantitative monitoring to make sure it stays there, are what would be necessary. In other words, for populations with reasonable average numbers of HIV-infected partners, given the will and effort, it is within our means to halt this epidemic using condoms.
虽然治疗战略似乎有望延缓艾滋病毒相关疾病的发展,但预防仍然是防治艾滋病毒/艾滋病流行的最有效战略。本文的重点是在没有任何治疗的情况下,使用避孕套作为预防艾滋病毒的单一策略方法的效果。使用避孕套制止艾滋病毒/艾滋病流行有两个主要因素:避孕套的功效和遵守规定。本文通过建立一个新的确定性数学模型,重点研究了这些因素对阻止疫情的影响。根据最新的荟萃分析,目前避孕套预防艾滋病毒传播的有效性估计为60-96%,平均值为87%。由于参数估计受到各种不确定性的影响,为了充分保证预测的质量,采用拉丁超立方抽样(LHS)和偏秩相关系数(prcc)进行不确定性和敏感性分析。利用稳定性和敏感性分析,基于合理的参数值范围,确定了控制HIV持续存在或根除的关键参数。这一分析表明,我们称之为“可预防性”的效力和依从性的产物对流行病具有负面影响;随着p值的增加,流行程度降低。研究还表明,阈值可预防性随着易感个体,特别是处于艾滋病阶段的易感个体的平均艾滋病毒感染伴侣数量的增加而增加。对于感染艾滋病毒的伴侣平均人数很多的人群,相关的可预防门槛很高,可能无法达到,这表明,对于这样的人群,可能无法仅使用避孕套来控制艾滋病毒。另一方面,对于感染艾滋病毒的伴侣平均人数较低(在合理范围内)的人口,pc约为75%,这表明可以使用避孕套来阻止这种流行病。因此,对于这样的人群,有必要采取公共卫生措施,将可预防性提高到阈值以上,并进行持续的定量监测,以确保其保持在阈值以上。换句话说,对于那些伴侣感染艾滋病毒的平均人数合理的人来说,只要有意愿和努力,我们就有能力使用避孕套来制止这种流行病。
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引用次数: 43
Formation of Vertebral Precursors: Past Models and Future Predictions 椎体前体的形成:过去的模型和未来的预测
Pub Date : 2003-03-01 DOI: 10.1080/10273660310001628365
R. Baker, S. Schnell, P. Maini
Disruption of normal vertebral development results from abnormal formation and segmentation of the vertebral precursors, called somites. Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. We review the most popular models of somite formation: Cooke and Zeeman’s clock and wavefront model, Meinhardt’s reaction –diffusion model and the cell cycle model of Stern and co-workers, and discuss the consistency of each in the light of recent experimental findings concerning FGF-8 signalling in the presomitic mesoderm (PSM). We present an extension of the cell cycle model to take account of this new experimental evidence, which shows the existence of a determination front whose position in the PSM is controlled by FGF-8 signalling, and which controls the ability of cells to become competent to segment. We conclude that it is, at this stage, perhaps erroneous to favour one of these models over the others.
正常椎体发育的中断是由于椎体前体(体体)的异常形成和分割造成的。体细胞发育是沿脊椎动物胚胎前后轴周期性模式的顺序形成,是胚胎发生过程中最明显的片段模式过程之一,也是发育生物学中未解决的主要问题之一。我们回顾了最流行的体形成模型:Cooke和Zeeman的时钟和波前模型,Meinhardt的反应-扩散模型和Stern及其同事的细胞周期模型,并根据最近关于体前中胚层(PSM)中FGF-8信号传导的实验发现讨论了每种模型的一致性。我们提出了细胞周期模型的扩展,以考虑到这一新的实验证据,这表明存在一个决定前沿,其在PSM中的位置由FGF-8信号控制,并控制细胞变得有能力分裂的能力。我们的结论是,在现阶段,偏爱其中一种模式而不喜欢其他模式可能是错误的。
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引用次数: 21
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Journal of Theoretical Medicine
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