XXIst century magnetotherapy

Abstract

This paper discusses the state of the art therapeutic application of magnetic and electromagnetic fields (EMF) in treatment of various medical problems – from pain relief to musculoskeletal trauma, to vascular and endocrine disorders. The paper describes problems related to physical parameters of used fields, biophysical dosimetry, clinical protocols, and safety of the device operators. Clinical benefits and mechanisms of action are also discussed.     

Microwave generation by a superluminal source at limiting current densities

It is well known that high-power directed wideband electromagnetic radiation in the microwave range can be generated by a superluminal pulse of the electron emission current. The operation of a simple emitting element driven by a superluminal current pulse and consisting of an accelerating diode with a photocathode and a source of ionizing radiation that initiates electron emission from the cathode is considered. It is shown that the parameters of an elementary superluminal source obey scaling relations that are determined by the growth rate of the electron emission current from the photocathode and the parameters of the accelerating diode. The limiting anode current density and the limiting values of the characteristics of electromagnetic radiation achievable in such a system are determined. The effect of the finite dimensions of the accelerating system on the parameters of the emitter is investigated, and the spatiotemporal characteristics of the generated electromagnetic fields are obtained.     

Computer simulation of cell renewal systems]

This paper deals with a block diagram which describes the structure of the control of erythropoiesis by negative feedback loops. The model is transformed into an adequate simulation program using a special block-oriented programming language called ASIM (Analoge SIMulation). For both normal and diseased states of the blood forming process the dynamic responses of the erythrocytes and reticulocytes are simulated by a digital computer analysis. The computer simulation includes different forms of anemia caused by parameter variations as well as by structural alterations. Rising oscillations are obtained too in multiloop control systems containing complex paths with minor loops, which for example take into account the erythrocytic chalones. The described model shows that rising oscillations, that are unstable control loops, can be produced by changing the control-loop structure as well as by parameter changes. In case of malignant disorders such failures becoming effective in oscillations are discussed as parts of disturbed homoeostasis. The results of these studies obtained by simulation should especially stimulate scientists working in the fields of biology and medicine to new test series to verify the proposed hypothesis.     

Recent advances in maximum entropy biasing techniques for molecular dynamics

ABSTRACT

This review describes recent advances by the authors and others on the topic of incorporating experimental data into molecular simulations through maximum entropy methods. Methods which incorporate experimental data improve accuracy in molecular simulation by minimally modifying the thermodynamic ensemble. This is especially important where force fields are approximate, such as when employing coarse-grain models, or where high accuracy is required, such as when attempting to mimic a multiscale self-assembly process. The authors review here the experiment directed simulation (EDS) and experiment directed metadynamics (EDM) methods that allow matching averages and distributions in simulations, respectively. Important system-specific considerations are discussed such as using enhanced sampling simultaneously, the role of pressure, treating uncertainty, and implementations of these methods. Recent examples of EDS and EDM are reviewed including applications to ab initio molecular dynamics of water, incorporating environmental fluctuations inside of a macromolecular protein complex, improving RNA force fields, and the combination of enhanced sampling with minimal biasing to model peptides     

Modeling of the photosynthetic electron transport regulation in cyanobacteria

In this work we have performed a computer analysis of electron and proton transport in cyanobacterial cells using a mathematical model of light-dependent stages of photosynthesis taking into account the key stages of pH-dependent regulation of electron transport on both acceptor and donor sides of photosystem 1 (PS1). Comparison of theoretical and experimental data shows that the model adequately describes the multiphase kinetics of photoinduced redox transformations of P₇₀₀ (the primary electron donor in PS1). Our computer simulation describes the effect of variations of atmospheric gases (CO₂ and O₂) on the induction events in cyanobacteria (P₇₀₀ photooxidation, generation of transmembrane ΔpH), which strongly depends on the preillumination conditions (aerobic or anaerobic atmosphere). It has been shown that the variations of CO₂ concentration in the cell interior may noticeably affect the kinetics of electron transport, acidification of lumen, and ATP synthesis. The contributions of alternative pathways of electron transport (cyclic electron transport around PS1 and electron outflow to O₂) to the function of cyanobacterial photosynthetic apparatus have been analyzed. At the initial stage of induction period, cyclic electron flows around PS1 (“short” and “long” pathways) substantially contribute to photosynthetic electron transport. These flows, however, attenuate with the light-induced activation of the Calvin-Benson cycle reactions. In the meantime, the outflow of electrons from PS1 to O₂ (or to other metabolic chains) increases with oxygen accumulation in the medium. The effects of ferredoxin oxidation by hydrogenase catalyzing the H₂ formation on the kinetics of P700 photooxidation and distribution of electron flows on the acceptor side of PS1 have been modeled.     

Spatiotemporal modeling and analysis of transient gene delivery

A quantitative and mechanistic understanding of intracellular transport processes in eukaryotic cells during transient transfection is an important prerequisite for the systematic and specific optimization of transient gene expression procedures for pharmaceutic and industrial protein production. There is evidence that intracellular transport processes during gene delivery and their regulation may have significant influence on the transfection efficiency. This contribution describes a compartmented, spatiotemporally resolved and stochastic modeling approach that describes intracellular transport processes responsible for gene delivery during transient transfection. It enables a detailed prediction and analysis and identification of potential bottlenecks. This model is currently being adapted to a model cell line, HEK293s. The simulated results are compared with experimental quantitative polymerase chain reaction (qPCR) data and confocal imaging data obtained with transfected and stained HEK293 cells. Global parameter estimation is performed to qPCR data based on two different novel plasmid constructs in order to identify candidates for plasmid-specific transport parameter variations. The influence of the specific property of HEK293 cells to grow in clusters is investigated and the impact of active microtubule transport depending on cell morphology and clustering is examined. A general sensitivity analysis allows for the identification of the sensitive parameters.     

Simulations of tokamak discharges with fast L-H transitions

Results are presented from the simulations of discharges with fast L-H transitions in the JET tokamak. During a transition, electron temperature perturbations propagate into the plasma core over a time much shorter than the transport time characteristic of this device. It is shown that the experimentally observed variations in the electron temperature may be caused by the change in the particle source intensity in the plasma when the atomic flux decreases, which is detected from the drop in the intensity of the D_α hydrogen spectral line. Hence, the experiments under consideration can be explained without the assumption about the nonlocal character of transport processes in tokamaks, which was made in some papers devoted to JET experiments. The plasma component responsible for the apparent nonlocal character of transport processes is the neutral component, whose propagation time across the plasma column is sufficiently short (t<100 μs). __________ Translated from Fizika Plazmy, Vol. 28, No. 1, 2002, pp. 3–8. Original Russian Text Copyright ? 2002 by Leonov.     

Theory of the ICR heating of a plasma column: Methodological note

A set of wave equations is derived that describes electromagnetic waves at frequencies on the order of the ion gyrofrequency in a plasma column with an arbitrary electron temperature. This set takes into account, in particular, the resonant interaction of electrons with waves in the transit-time magnetic pumping regime. The effect of the amplification of the electromagnetic fields of current-carrying antennas by the plasma is analyzed. The evolution of the fields with an increase of plasma density from a zero value (vacuum) is considered. The main parameters are determined for minority ion cyclotron resonance heating in the planned EPSILON system.     

Simulation of electron beam formation and transport in a gas-filled electron-optical system with a plasma emitter

The results of computer simulations of the electron-optical system of an electron gun with a plasma emitter are presented. The simulations are performed using the KOBRA3-INP, XOOPIC, and ANSYS codes. The results describe the electron beam formation and transport. The electron trajectories are analyzed. The mechanisms of gas influence on the energy inhomogeneity of the beam and its current in the regions of beam primary formation, acceleration, and transport are described. Recommendations for optimizing the electron-optical system with a plasma emitter are presented.     

ESTIMATION OF THE PHYSIOLOGICAL PARAMETERS OF A MEMBRANE CHANNEL EXPOSED TO ELECTROMAGNETIC FIELDS USING THE GPOF APPROACH

A method is proposed for the estimation of kinetic parameters of ionic channels in the cell membrane. The method is based on the generalized pencil-of-function approach, which exploits transient current signals from single channels to derive the frequency of the system poles. The proposed approach is validated for the well-known potassium channel by comparing the estimated values with the theoretical values given by Hodgkin and Huxley. The approach is superior to previous spectral approaches, both for its accuracy and for its robustness. It is especially useful for parameter estimation when the channel is exposed to electromagnetic fields. Results are given for exposure to 200-Hz and 915-MHz signals, to demonstrate the effect of fields on the kinetic parameters of the channel.     

电磁场曝露对生物组织电磁特性的影响

电磁辐射严重影响着人体的健康.电磁场生物效应的发生机制与电磁场本身的特性相关,同时也与生物组织在电磁场作用下电磁特性的改变密切相关.生物体内的信号分子、自由基以及磁颗粒等处于外加电磁场中时其电磁特性会发生变化,尤其是不同频率电磁场曝露作用下生物组织的导电、介电以及磁学等特性会有非常显著的区别.明确不同频率电磁场作用下生物组织电磁特性的变化规律是研究电磁场生物效应发生机制以及预防问题的关键.综述了近年来电磁场对于生物组织电磁特性影响的研究成果,并对未来的研究方向做了展望.     

Designing Electromagnetic Field Rotators with Homogenous and Isotropic Materials

This paper reports the design features of an electromagnetic device with an improved mapping transformation function allowing perfect electromagnetic rotation. Based on transformation optics theory, theoretical analysis has been used to show the constitutive parameters of both unimproved and improved perfect case which has ultimately validated via full-wave simulations. For implementation of this device, an alternating structure of zero-index metamaterials and perfect electric conductors has been used. The functionality of the proposed structure was verified by numerical simulations.

     

Effect of Salts and Electron Transport on the Conformation of Isolated Chloroplasts. II. Electron Microscopy

Spinach chloroplasts isolated in media containing salts and the rare chloroplasts which are still within their envelopes alike retain grana similar to those seen in chloroplasts in situ.

Chloroplasts isolated in low-salt media lose their grana without losing any chlorophyll. These grana-free chloroplasts are considerably swollen and consist almost entirely of continuous sheets of paired-membrane structures. These double structures, the lamellae, are only loosely held together, primarily at the edges, by tenuous material which does not react with permanganate.

Addition of salts (methylamine hydrochloride, NaCl, MgCl₂) to the grana-free low-salt chloroplasts provide strong interlamellar attractions. These attractions result in a stacking of the lamellae which is sometimes almost random but sometimes results in regular structures indistinguishable from the original grana.

The phosphorylation-uncoupler atebrin causes further swelling of the chloroplasts in the absence of electron transport by increasing the space between the paired membranes of the lamellae.

The rapid electron transport (Hill reaction) made possible by atebrin-uncoupling is associated with a great decrease in chloroplast volume. This decrease results from a collapsing together of the widely separated lamellar membrane pairs. The pairs approach each other so closely that they usually appear as a single membrane when viewed with the electron microscope. The much slower electron transport which occurs in the absence of uncouplers is associated with a similar but smaller decrease in the space between the lamellar membrane pairs.

Chloroplasts swell during the rapid electron transport made possible by the phosphorylation-uncoupler methylamine. This swelling is accompanied by a degree of membrane distortion which precludes an interpretation of the mechanism. As with atebrin-faciliated electron transport, obviously paired membranes disappear but it is not yet clear whether this is by association or dissociation of the pairs.

     

Imidazolium‐Substituted Polythiophenes as Efficient Electron Transport Materials Improving Photovoltaic Performance

In the field of polymer solar cells, improving photovoltaic performance has been the main driver over the past decade. To achieve high power conversion efficiencies, a plethora of new photoactive donor polymers and fullerene derivatives have been developed and blended together in bulk heterojunction active layers. Simultaneously, further optimization of the device architecture is also of major importance. In this respect, we report on the use of specific types of electron transport layers to boost the inherent I–V properties of polymer solar cell devices, resulting in a considerable gain in overall photovoltaic output. Imidazolium‐substituted polythiophenes are introduced as appealing electron transport materials, outperforming the currently available analogous conjugated polyelectrolytes, mainly by an increase in short‐circuit current. The molecular weight of the ionic polythiophenes has been identified as a crucial parameter influencing performance.     

Radio frequency electromagnetic exposure: Tutorial review on experimental dosimetry

Radio frequency (RF) dosimetry is the quantification of the magnitude and distribution of absorbed electromagnetic energy within biological objects that are exposed to RF fields. At RF, the dosimetric quantity, which is called the specific absorption rate (SAR), is defined as the rate at which energy is absorbed per unit mass. The SAR is determined not only by the incident electromagnetic waves but also by the electrical and geometric characteristics of the irradiated subject and nearby objects. It is related to the internal electric field strength (E) as well as to the electric conductivity and the density of tissues; therefore, it is a suitable dosimetric parameter, even when a mechanism is determined to be “athermal.” SAR distributions are usually determined from measurements in human models, in animal tissues, or from calculations. This tutorial describes experimental techniques that are used commonly to determine SAR distributions along with the SAR limitations and unresolved problems. The methods discussed to obtain point, planar, or whole-body averaged SARs include the use of small E-field probes or measurement of initial rate of temperature rise in an irradiated object. © 1996 Wiley-Liss, Inc.     

Optical Properties of Metallic Nanotubes with Broken Symmetry: Detection of Eccentricity

The optical properties of dielectric core-metallic concentric shell nanoparticles show a highly sensitive dependence on geometrical parameters of the system. It is due to the strong interaction between plasmon modes excited on the surfaces of the metallic shell. Perturbations in the symmetries of the system modify these interactions and enable new ones, giving rise to dramatic variations in the far field spectrum. In this paper, we examine the electromagnetic response (far and near fields) of hollow metallic nanotubes (nts) with empty or dielectric core as a function of the offset parameter between the core and the shell. The evolution of extinction spectra shows a strong redshift for the dipolar resonance when the offset parameter is increasing, whereas new multipole interactions can be observed at high energy. As dimers, the extinction cross section for nts with nonhomogeneous shell thickness depends on incidence angle with respect to offset axis. We show that for a given offset, the lowest energy peak in extinction curves experiences both, a blueshift and increase of intensity when the angle of incidence is varied with respect to the axis of eccentricity. Maxima of both intensity and blueshift are achieved for an incidence perpendicular to the axis of eccentricity. We show that the optical properties provide sufficient information to unambiguously characterize the system. To compute the electromagnetic field at any point in space, we implemented a rigorous integral formalism (2D geometry) for the two fundamental modes of polarization (s and p modes).     

Effect of Blood Vessel Segmentation on the Outcome of Electroporation-Based Treatments of Liver Tumors

Electroporation-based treatments rely on increasing the permeability of the cell membrane by high voltage electric pulses applied to tissue via electrodes. To ensure that the whole tumor is covered with sufficiently high electric field, accurate numerical models are built based on individual patient anatomy. Extraction of patient''s anatomy through segmentation of medical images inevitably produces some errors. In order to ensure the robustness of treatment planning, it is necessary to evaluate the potential effect of such errors on the electric field distribution. In this work we focus on determining the effect of errors in automatic segmentation of hepatic vessels on the electric field distribution in electroporation-based treatments in the liver. First, a numerical analysis was performed on a simple ''sphere and cylinder'' model for tumors and vessels of different sizes and relative positions. Second, an analysis of two models extracted from medical images of real patients in which we introduced variations of an error of the automatic vessel segmentation method was performed. The results obtained from a simple model indicate that ignoring the vessels when calculating the electric field distribution can cause insufficient coverage of the tumor with electric fields. Results of this study indicate that this effect happens for small (10 mm) and medium-sized (30 mm) tumors, especially in the absence of a central electrode inserted in the tumor. The results obtained from the real-case models also show higher negative impact of automatic vessel segmentation errors on the electric field distribution when the central electrode is absent. However, the average error of the automatic vessel segmentation did not have an impact on the electric field distribution if the central electrode was present. This suggests the algorithm is robust enough to be used in creating a model for treatment parameter optimization, but with a central electrode.     

Modeling the electron transport chain of purple non‐sulfur bacteria

Purple non‐sulfur bacteria (Rhodospirillaceae) have been extensively employed for studying principles of photosynthetic and respiratory electron transport phosphorylation and for investigating the regulation of gene expression in response to redox signals. Here, we use mathematical modeling to evaluate the steady‐state behavior of the electron transport chain (ETC) in these bacteria under different environmental conditions. Elementary‐modes analysis of a stoichiometric ETC model reveals nine operational modes. Most of them represent well‐known functional states, however, two modes constitute reverse electron flow under respiratory conditions, which has been barely considered so far. We further present and analyze a kinetic model of the ETC in which rate laws of electron transfer steps are based on redox potential differences. Our model reproduces well‐known phenomena of respiratory and photosynthetic operation of the ETC and also provides non‐intuitive predictions. As one key result, model simulations demonstrate a stronger reduction of ubiquinone when switching from high‐light to low‐light conditions. This result is parameter insensitive and supports the hypothesis that the redox state of ubiquinone is a suitable signal for controlling photosynthetic gene expression.     

Comparing performances of logistic regression and neural networks for predicting melatonin excretion patterns in the rat exposed to ELF magnetic fields

Various studies have been reported on the bioeffects of magnetic field exposure; however, no consensus or guideline is available for experimental designs relating to exposure conditions as yet. In this study, logistic regression (LR) and artificial neural networks (ANNs) were used in order to analyze and predict the melatonin excretion patterns in the rat exposed to extremely low frequency magnetic fields (ELF‐MF). Subsequently, on a database containing 33 experiments, performances of LR and ANNs were compared through resubstitution and jackknife tests. Predictor variables were more effective parameters and included frequency, polarization, exposure duration, and strength of magnetic fields. Also, five performance measures including accuracy, sensitivity, specificity, Matthew's Correlation Coefficient (MCC) and normalized percentage, better than random (S) were used to evaluate the performance of models. The LR as a conventional model obtained poor prediction performance. Nonetheless, LR distinguished the duration of magnetic fields as a statistically significant parameter. Also, horizontal polarization of magnetic fields with the highest logit coefficient (or parameter estimate) with negative sign was found to be the strongest indicator for experimental designs relating to exposure conditions. This means that each experiment with horizontal polarization of magnetic fields has a higher probability to result in “not changed melatonin level” pattern. On the other hand, ANNs, a more powerful model which has not been introduced in predicting melatonin excretion patterns in the rat exposed to ELF‐MF, showed high performance measure values and higher reliability, especially obtaining 0.55 value of MCC through jackknife tests. Obtained results showed that such predictor models are promising and may play a useful role in defining guidelines for experimental designs relating to exposure conditions. In conclusion, analysis of the bioelectromagnetic data could result in finding a relationship between electromagnetic fields and different biological processes. Bioelectromagnetics 31:164–171, 2010. © 2009 Wiley‐Liss, Inc.