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用于解释生物系统暴露于弱相互作用电磁场的实验的分子变化信噪比标准。

Molecular change signal-to-noise criteria for interpreting experiments involving exposure of biological systems to weakly interacting electromagnetic fields.

作者信息

Vaughan Timothy E, Weaver James C

机构信息

Harvard-M.I.T. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

出版信息

Bioelectromagnetics. 2005 May;26(4):305-22. doi: 10.1002/bem.20094.

Abstract

We describe an approach to aiding the design and interpretation of experiments involving biological effects of weakly interacting electromagnetic fields that range from steady (dc) to microwave frequencies. We propose that if known biophysical mechanisms cannot account for an inferred, underlying molecular change signal-to-noise ratio, (S/N)gen, of a observed result, then there are two interpretation choices: (1) there is an unknown biophysical mechanism with stronger coupling between the field exposure and the ongoing biochemical process, or (2) the experiment is responding to something other than the field exposure. Our approach is based on classical detection theory, the recognition that weakly interacting fields cannot break chemical bonds, and the consequence that such fields can only alter rates of ongoing, metabolically driven biochemical reactions, and transport processes. The approach includes both fundamental chemical noise (molecular shot noise) and other sources of competing chemical change, to be compared quantitatively to the field induced change for the basic case that the field alters a single step in a biochemical network. Consistent with pharmacology and toxicology, we estimate the molecular dose (mass associated with field induced molecular change per mass tissue) resulting from illustrative low frequency field exposures for the biophysical mechanism of voltage gated channels. For perspective, we then consider electric field-mediated delivery of small molecules across human skin and into individual cells. Specifically, we consider the examples of iontophoretic and electroporative delivery of fentanyl through skin and electroporative delivery of bleomycin into individual cells. The total delivered amount corresponds to a molecular change signal and the delivery variability corresponds to generalized chemical noise. Viewed broadly, biological effects due to nonionizing fields may include animal navigation, medical applications, and environmental hazards. Understanding necessary conditions for such effects can be based on a unified approach: quantitative comparison of the estimated chemical change due to a particular electromagnetic field exposure to that due to competing influences, with both estimates based on a biophysical mechanism model within the context of a model of a biological system.

摘要

我们描述了一种方法,用于辅助设计和解释涉及从稳定(直流)到微波频率的弱相互作用电磁场生物效应的实验。我们提出,如果已知的生物物理机制无法解释观测结果中推断的潜在分子变化信噪比(S/N)gen,那么有两种解释选择:(1)存在一种未知的生物物理机制,在场暴露与正在进行的生化过程之间具有更强的耦合,或者(2)实验响应的是场暴露之外的其他因素。我们的方法基于经典检测理论、弱相互作用场不能破坏化学键的认识,以及这种场只能改变正在进行的、代谢驱动的生化反应速率和传输过程的结果。该方法包括基本化学噪声(分子散粒噪声)和其他竞争性化学变化源,以便在电磁场改变生化网络中单个步骤的基本情况下,将其与场诱导变化进行定量比较。与药理学和毒理学一致,我们针对电压门控通道的生物物理机制,估计了说明性低频场暴露所产生的分子剂量(每质量组织与场诱导分子变化相关的质量)。为了提供背景信息,我们接着考虑电场介导小分子穿过人体皮肤并进入单个细胞的情况。具体而言,我们考虑了通过皮肤离子电渗和电穿孔递送芬太尼以及将博来霉素电穿孔递送至单个细胞的例子。总递送量对应于分子变化信号,而递送变异性对应于广义化学噪声。从广义上看,非电离场引起的生物效应可能包括动物导航、医学应用和环境危害。理解此类效应的必要条件可以基于一种统一的方法:将特定电磁场暴露引起的估计化学变化与竞争影响引起的估计化学变化进行定量比较,这两种估计均基于生物系统模型背景下的生物物理机制模型。

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