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On fractional order models for Hepatitis C. 关于丙型肝炎的分数阶模型
Pub Date : 2010-03-18 DOI: 10.1186/1753-4631-4-1
E Ahmed, H A El-Saka

In this paper we present a fractional order generalization of Perelson et al. basic hepatitis C virus (HCV) model including an immune response term. We argue that fractional order equations are more suitable than integer order ones in modeling complex systems which include biological systems. The model is presented and discussed. Also we argue that the added immune response term represents some basic properties of the immune system and that it should be included to study longer term behavior of the disease.

在本文中,我们介绍了 Perelson 等人的丙型肝炎病毒(HCV)基本模型的分数阶一般化,其中包括一个免疫反应项。我们认为,在包括生物系统在内的复杂系统建模中,分数阶方程比整数阶方程更合适。我们对模型进行了介绍和讨论。此外,我们还认为,添加的免疫反应项代表了免疫系统的一些基本特性,因此应将其包含在内,以研究疾病的长期行为。
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引用次数: 0
On managing complex adaptive systems motivated by biosystems application to infections. 关于管理由生物系统应用于感染引起的复杂适应系统。
Pub Date : 2009-10-12 DOI: 10.1186/1753-4631-3-11
As Hegazi, Ah Hashish, E Ahmed

Many attempts to control Complex adaptive systems (CAS) have failed. Here we try to learn from biosystems to derive some principles for CAS management. An application to managing infections is given.

许多控制复杂自适应系统(CAS)的尝试都失败了。在此,我们试图从生物系统中学习,得出CAS管理的一些原则。给出了一种控制感染的应用。
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引用次数: 3
Influence of very low doses of mediators on fungal laccase activity - nonlinearity beyond imagination. 极低剂量介质对真菌漆酶活性的影响——超出想象的非线性。
Pub Date : 2009-09-04 DOI: 10.1186/1753-4631-3-10
Elzbieta Malarczyk, Janina Kochmanska-Rdest, Anna Jarosz-Wilkolazka

Laccase, an enzyme responsible for aerobic transformations of natural phenolics, in industrial applications requires the presence of low-molecular substances known as mediators, which accelerate oxidation processes. However, the use of mediators is limited by their toxicity and the high costs of exploitation. The activation of extracellular laccase in growing fungal culture with highly diluted mediators, ABTS and HBT is described. Two high laccase-producing fungal strains, Trametes versicolor and Cerrena unicolor, were used in this study as a source of enzyme. Selected dilutions of the mediators significantly increased the activity of extracellular laccase during 14 days of cultivation what was distinctly visible in PAGE technique and in colorimetric tests. The same mediator dilutions increased demethylation properties of laccase, which was demonstrated during incubation of enzyme with veratric acid. It was established that the activation effect was assigned to specific dilutions of mediators. Our dose-response dilution process smoothly passes into the range of action of homeopathic dilutions and is of interest for homeopaths.

漆酶是一种负责天然酚类有氧转化的酶,在工业应用中需要被称为介质的低分子物质的存在,这种介质可以加速氧化过程。然而,介质的使用受到其毒性和开发成本高的限制。本文描述了用高度稀释的培养基ABTS和HBT培养真菌时细胞外漆酶的激活情况。本研究以两种高产漆酶的真菌菌株,versicoltrametes和Cerrena unicolor作为酶的来源。在14天的培养过程中,选定的稀释培养基显著增加了细胞外漆酶的活性,这在PAGE技术和比色试验中是明显可见的。同样的介质稀释增加了漆酶的去甲基化特性,这在酶与戊二酸的孵育过程中得到了证明。结果表明,活化效应与特定稀释度的介质有关。我们的剂量反应稀释过程顺利进入顺势疗法稀释的作用范围,是顺势疗法的兴趣。
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引用次数: 17
Disturbed functional brain networks and neurocognitive function in low-grade glioma patients: a graph theoretical analysis of resting-state MEG. 低级别胶质瘤患者脑功能网络和神经认知功能紊乱:静息状态脑磁图图理论分析。
Pub Date : 2009-08-23 DOI: 10.1186/1753-4631-3-9
Ingeborg Bosma, Jaap C Reijneveld, Martin Klein, Linda Douw, Bob W van Dijk, Jan J Heimans, Cornelis J Stam

Background: To understand neurophysiological mechanisms underlying cognitive dysfunction in low-grade glioma (LGG) patients by evaluating the spatial structure of 'resting-state' brain networks with graph theory.

Methods: Standardized tests measuring 6 neurocognitive domains were administered in 17 LGG patients and 17 healthy controls. Magnetoencephalography (MEG) recordings were conducted during eyes-closed 'resting state'. The phase lag index (PLI) was computed in seven frequency bands to assess functional connectivity between brain areas. Spatial patterns were characterized with graph theoretical measures such as clustering coefficient (local connectivity), path length (global integration), network small world-ness (ratio of clustering coefficient/path length) and degree correlation (the extent to which connected nodes have similar degrees).

Results: Compared to healthy controls, patients performed poorer on psychomotor functioning, attention, information processing, and working memory. Patients displayed higher short- and long-distance synchronization and clustering coefficient in the theta band, whereas a lower clustering coefficient and small world-ness were observed in the beta band. A lower degree correlation was found in the upper gamma band. LGG patients with higher clustering coefficient, longer path length, and lower degree correlations in delta and lower alpha band were characterized by poorer neurocognitive performance.

Conclusion: LGG patients display higher short- and long-distance synchronization within the theta band. Network analysis revealed changes (in particularly the theta, beta, and upper gamma band) suggesting disturbed network architecture. Moreover, correlations between network characteristics and neurocognitive performance were found, Widespread changes in the strength and spatial organization of brain networks may be responsible for cognitive dysfunction in glioma patients.

背景:利用图论评价脑“静息状态”网络的空间结构,了解低级别胶质瘤(LGG)患者认知功能障碍的神经生理机制。方法:对17例LGG患者和17例健康对照者进行6个神经认知域的标准化测试。在闭眼“静息状态”下进行脑磁图(MEG)记录。计算7个频段的相位滞后指数(PLI)来评估脑区之间的功能连通性。通过图论度量,如聚类系数(局部连通性)、路径长度(全局整合)、网络小世界性(聚类系数/路径长度之比)和关联度(连接节点具有相似度的程度)来表征空间模式。结果:与健康对照组相比,患者在精神运动功能、注意力、信息处理和工作记忆方面表现较差。患者在θ波段表现出较高的短距离和远距离同步性和聚类系数,而在β波段表现出较低的聚类系数和小世界性。在上伽马波段发现了较低程度的相关性。聚类系数较高、路径长度较长、δ和下α波段关联度较低的LGG患者神经认知表现较差。结论:LGG患者在theta波段有较高的短距离和远距离同步。网络分析揭示了变化(特别是θ、β和上γ波段),表明网络架构受到了干扰。此外,神经网络特征与神经认知表现之间存在相关性。脑网络强度和空间组织的广泛变化可能是神经胶质瘤患者认知功能障碍的原因。
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引用次数: 130
Extracting complexity waveforms from one-dimensional signals. 从一维信号中提取复杂波形。
Pub Date : 2009-08-14 DOI: 10.1186/1753-4631-3-8
Aleksandar Kalauzi, Tijana Bojić, Ljubisav Rakić

Background: Nonlinear methods provide a direct way of estimating complexity of one-dimensional sampled signals through calculation of Higuchi's fractal dimension (1

Results: In this work we propose a new and simple way to estimate FD for N < 100 by introducing 'normalized length density' of a signal epoch,where yn(i) represents the ith signal sample after amplitude normalization. The actual calculation of signal FD is based on construction of a monotonic calibration curve, FD = f(NLD), on a set of Weierstrass functions, for which FD values are given theoretically. The two existing methods, Higuchi's and consecutive differences, applied simultaneously on signals with constant FD (white noise and Brownian motion), showed that standard deviation of calculated window FD (FDw) increased sharply as the epoch became shorter. However, in case of the new NLD method a considerably lower scattering was obtained, especially for N < 30, at the expense of some lower accuracy in calculating average FDw. Consequently, more accurate reconstruction of FD waveforms was obtained when synthetic signals were analyzed, containig short alternating epochs of two or three different FD values. Additionally, scatter plots of FDw of an occipital human EEG signal for 10 sample epochs demontrated that Higuchi's estimations for some epochs exceeded the theoretical FD limits, while NLD-derived values did not.

Conclusion: The presented approach was more accurate than the existing two methods in FD(t) extraction for very short epochs and could be used in physiological signals when FD is expected to change abruptly, such as short phasic phenomena or transient artefacts, as well as in other fields of science.

背景:非线性方法通过计算Higuchi分形维数提供了一种估计一维采样信号复杂性的直接方法(结果:在这项工作中,我们提出了一种新的简单方法,通过引入信号历元的“归一化长度密度”来估计N < 100的FD,其中yn(i)表示幅度归一化后的第i个信号样本。信号FD的实际计算是基于在一组Weierstrass函数上构造单调校准曲线FD = f(NLD),并在理论上给出该函数的FD值。现有的Higuchi和连续差分两种方法同时应用于FD(白噪声和布朗运动)不变的信号,结果表明,计算窗口FD (FDw)的标准差随着历元的缩短而急剧增大。然而,对于新的NLD方法,特别是当N < 30时,获得了相当低的散射,但代价是计算平均FDw的精度有所降低。因此,当分析含有两个或三个不同FD值的短交替周期的合成信号时,可以获得更精确的FD波形重建。另外,枕部脑电图信号的10个epoch的FDw散点图表明,Higuchi的估计在某些epoch超过了理论FD极限,而nld的推导值则没有。结论:该方法在极短周期的FD(t)提取上比现有两种方法更准确,可用于FD可能突然变化的生理信号,如短相位现象或瞬态伪影,以及其他科学领域。
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引用次数: 18
Simulation study of autoregulation responses of peripheral circulation to systemic pulsatility. 外周循环对全身搏动的自动调节反应的模拟研究。
Pub Date : 2009-07-24 DOI: 10.1186/1753-4631-3-7
Federico Aletti, Ettore Lanzarone, Maria Laura Costantino, Giuseppe Baselli

Background: This simulation study investigated potential modulations of total peripheral resistance (TPR), due to distributed peripheral vascular activity, by means of a lumped model of the arterial tree and a non linear model of microcirculation, inclusive of local controls of blood flow and tissue-capillary fluid exchange.

Results: Numerical simulations of circulation were carried out to compute TPR under different conditions of blood flow pulsatility, and to extract the pressure-flow characteristics of the cardiovascular system. Simulations showed that TPR seen by the large arteries was increased in absence of pulsatility, while it decreased with an augmented harmonic content. This is a typically non linear effect due to the contribution of active, non linear autoregulation of the peripheral microvascular beds, which also generated a nonlinear relationship between arterial blood pressure and cardiac output.

Conclusion: This simulation study, though focused on a simple effect attaining TPR modulation due to pulsatility, suggests that non-linear autoregulation mechanisms cannot be overlooked while studying the integrated behavior of the global cardiovascular system, including the arterial tree and the peripheral vascular bed.

背景:本模拟研究通过动脉树的集总模型和微循环的非线性模型,包括局部控制的血流和组织-毛细血管流体交换,研究了由于分布的外周血管活动而引起的总外周阻力(TPR)的潜在调节。结果:进行循环数值模拟,计算不同血流脉动度条件下的TPR,提取心血管系统的压力-流量特征。模拟结果表明,在没有搏动性的情况下,大动脉的TPR增加,而随着谐波含量的增加,TPR降低。这是一种典型的非线性效应,由于外周微血管床的主动、非线性自调节的贡献,这也产生了动脉血压和心输出量之间的非线性关系。结论:这项模拟研究虽然关注的是由脉搏性引起的TPR调节的简单效应,但表明在研究包括动脉树和外周血管床在内的全球心血管系统的综合行为时,非线性自调节机制不可忽视。
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引用次数: 7
Comparative study of nonlinear properties of EEG signals of normal persons and epileptic patients. 正常人与癫痫患者脑电图信号非线性特性的比较研究。
Pub Date : 2009-07-20 DOI: 10.1186/1753-4631-3-6
Md Nurujjaman, Ramesh Narayanan, An Sekar Iyengar

Background: Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent.

Results: Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak et al. [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases.

Conclusion: In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation.

背景:研究大脑在生命系统中的功能一直是科学家和医学从业者的主要努力。在各种大脑疾病中,癫痫引起了最多的关注,因为这种疾病会影响一个人的生活质量。本文应用代理分析、概率分布函数和赫斯特指数对正常和癫痫患者的脑电图进行了重新研究。结果:采用随机shuffle替代分析,我们获得了Andrzejak等人[Phys Rev E 2001,64:06 - 1907]得到的癫痫患者癫痫发作时的一些非线性特征。概率分布函数表明癫痫病人的大脑活动在本质上是非高斯的。赫斯特指数已被证明对描述正常和癫痫大脑很有用它表明癫痫大脑是长期反相关的而正常大脑或多或少是随机的。在这里使用的所有技术中,赫斯特指数对于描述不同的情况非常有用。结论:本文主要用赫斯特指数显示正常人睁眼、闭眼、癫痫发作时和非发作期的特征差异。H表示正常人的大脑活动在本质上是不相关的,而癫痫患者的大脑活动则显示出长期的反相关。
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引用次数: 48
Using the nonlinear control of anaesthesia-induced hypersensitivity of EEG at burst suppression level to test the effects of radiofrequency radiation on brain function. 利用非线性控制猝发抑制水平的麻醉诱导脑电图超敏反应,测试射频辐射对大脑功能的影响。
Pub Date : 2009-07-18 DOI: 10.1186/1753-4631-3-5
Tarmo Lipping, Michael Rorarius, Ville Jäntti, Kari Annala, Ari Mennander, Rain Ferenets, Tommi Toivonen, Tim Toivo, Alpo Värri, Leena Korpinen

Background: In this study, investigating the effects of mobile phone radiation on test animals, eleven pigs were anaesthetised to the level where burst-suppression pattern appears in the electroencephalogram (EEG). At this level of anaesthesia both human subjects and animals show high sensitivity to external stimuli which produce EEG bursts during suppression. The burst-suppression phenomenon represents a nonlinear control system, where low-amplitude EEG abruptly switches to very high amplitude bursts. This switching can be triggered by very minor stimuli and the phenomenon has been described as hypersensitivity. To test if also radio frequency (RF) stimulation can trigger this nonlinear control, the animals were exposed to pulse modulated signal of a GSM mobile phone at 890 MHz. In the first phase of the experiment electromagnetic field (EMF) stimulation was randomly switched on and off and the relation between EEG bursts and EMF stimulation onsets and endpoints were studied. In the second phase a continuous RF stimulation at 31 W/kg was applied for 10 minutes. The ECG, the EEG, and the subcutaneous temperature were recorded.

Results: No correlation between the exposure and the EEG burst occurrences was observed in phase I measurements. No significant changes were observed in the EEG activity of the pigs during phase II measurements although several EEG signal analysis methods were applied. The temperature measured subcutaneously from the pigs' head increased by 1.6 degrees C and the heart rate by 14.2 bpm on the average during the 10 min exposure periods.

Conclusion: The hypothesis that RF radiation would produce sensory stimulation of somatosensory, auditory or visual system or directly affect the brain so as to produce EEG bursts during suppression was not confirmed.

背景:在这项调查移动电话辐射对试验动物影响的研究中,11 头猪被麻醉到脑电图(EEG)中出现突发性抑制模式的程度。在这种麻醉水平下,人类受试者和动物都会对外部刺激表现出高度敏感性,从而在抑制过程中产生脑电图脉冲串。猝发抑制现象代表了一种非线性控制系统,在这种系统中,低振幅脑电图会突然转换为极高振幅的猝发。这种切换可由非常轻微的刺激触发,这种现象被称为超敏反应。为了测试射频(RF)刺激是否也能触发这种非线性控制,我们将动物暴露在频率为 890 MHz 的 GSM 移动电话脉冲调制信号下。在实验的第一阶段,随机开启和关闭电磁场(EMF)刺激,研究脑电图突发与电磁场刺激的起始点和终点之间的关系。在第二阶段,31 W/kg 的连续射频刺激持续 10 分钟。对心电图、脑电图和皮下温度进行了记录:结果:在第一阶段的测量中,没有观察到暴露与脑电图突发之间的相关性。虽然采用了多种脑电信号分析方法,但在第二阶段的测量中没有观察到猪的脑电活动发生明显变化。在 10 分钟的暴露期间,从猪头部皮下测量到的体温平均上升了 1.6 摄氏度,心率平均上升了 14.2 bpm:射频辐射会对躯体感觉、听觉或视觉系统产生感官刺激,或直接影响大脑从而在抑制过程中产生脑电图脉冲的假设未得到证实。
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引用次数: 0
Critical scale of propagation influences dynamics of waves in a model of excitable medium. 临界传播尺度影响可激介质模型中波的动力学。
Pub Date : 2009-07-09 DOI: 10.1186/1753-4631-3-4
Joseph M Starobin, Christopher P Danford, Vivek Varadarajan, Andrei J Starobin, Vladimir N Polotski

Background: Duration and speed of propagation of the pulse are essential factors for stability of excitation waves. We explore the propagation of excitation waves resulting from periodic stimulation of an excitable cable to determine the minimal stable pulse duration in a rate-dependent modification of a Chernyak-Starobin-Cohen reaction-diffusion model.

Results: Various pacing rate dependent features of wave propagation were studied computationally and analytically. We demonstrated that the complexity of responses to stimulation and evolution of these responses from stable propagation to propagation block and alternans was determined by the proximity between the minimal level of the recovery variable and the critical excitation threshold for a stable solitary pulse.

Conclusion: These results suggest that critical propagation of excitation waves determines conditions for transition to unstable rhythms in a way similar to unstable cardiac rhythms. Established conditions were suitably accurate regardless of rate dependent features and the magnitude of the slopes of restitution curves.

背景:脉冲的传播时间和速度是影响激发波稳定性的重要因素。在Chernyak-Starobin-Cohen反应-扩散模型的速率相关修正中,我们探索了由可激发电缆的周期性刺激引起的激发波的传播,以确定最小稳定脉冲持续时间。结果:对不同起搏速率下的波传播特征进行了计算和分析研究。我们证明了刺激响应的复杂性以及这些响应从稳定传播到传播阻塞和交替的演变是由恢复变量的最小水平与稳定孤立脉冲的临界激励阈值之间的接近程度决定的。结论:这些结果表明,兴奋波的临界传播决定了向不稳定节律过渡的条件,其方式类似于不稳定心律。无论速率依赖特征和恢复曲线斜率的大小如何,所建立的条件都是适当准确的。
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引用次数: 3
Comments on introducing the immune system. 关于介绍免疫系统的评论。
Pub Date : 2009-06-11 DOI: 10.1186/1753-4631-3-3
E Ahmed

It is argued that by studying some design principles of the immune system, e.g. nonlinearity and being a complex adaptive system, one can easily find some explanations of basic properties of the system e.g. memory and tolerance.

本文认为,通过研究免疫系统的一些设计原理,如非线性和作为一个复杂的自适应系统,人们可以很容易地找到一些解释系统的基本特性,如记忆和耐受性。
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引用次数: 2
期刊
Nonlinear biomedical physics
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