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The influence of radiofrequency electromagnetic exposure on ligand binding to hydrophobic receptor proteins is a plausible early event of the interaction mechanism. A comprehensive quantum Zeeman-Stark model has been developed which takes into account the energy losses of the ligand ion due to its collisions inside the receptor crevice, the attracting nonlinear endogenous force due to the potential energy of the ion in the binding site, the out of equilibrium state of the ligand-receptor system due to the basal cell metabolism, and the thermal noise. The biophysical "output" is the change of the ligand binding probability that, in some instances, may be affected by a suitable low intensity exogenous electromagnetic "input" exposure, e.g., if the depth of the potential energy well of a putative receptor protein matches the energy of the radiofrequency photon. These results point toward both the possibility of the electromagnetic control of biochemical processes and the need for a new database of safety standards.

Biological tissues are ensembles of linear and nonlinear, symmetric and asymmetric constituents. As far as their electromagnetic characterization is concerned, they can be modeled as microscopic mixtures of the corresponding material media. Any medium volume can be properly discretized in a finite number of cells which can be modeled as an equivalent three dimensional network of lumped components, in order to characterize its electromagnetic behavior at wavelengths much longer than the relevant average linear size of the constitutive cells. Therefore, any mixture and the corresponding tissue can be characterized in terms of its effective conductance at extremely low frequency, with respect to a reference set of electrodes (ports of the equivalent network). When the above procedure is implemented for evaluating any of the aforesaid conductances, a resulting nonlinear characteristic should be expected. In reality, it may happen that the effect of the constitutive nonlinearities and the related asymmetries are smeared out by the randomness of the interconnections of the lumped components, leading at a macroscopic level to an isotropic constant equivalent conductance, i.e., to an isotropic constant equivalent conductivity of the mixture. The closed form analysis of a random network of nonlinear (piecewise linear) resistors offers a simple but clear cut example of such a property. This result, if extrapolated to biological media, suggests a new hint for explaining why there is no inconsistency between the typical electric characterization of biological tissues as almost linear macroscopic media, by means of their effective conductivity and permittivity, and the nonlinearities of the biochemical processes occurring in the tissue cells. In fact, the nonlinearities may not be observable by means of macroscopic electrical measurements because of the randomized spatial orientation and location of the processes.

Ultrasound has been proposed as a means to noninvasively assess bone and, particularly, bone strength and fracture risk. Although there has been some success in this application, there is still much that is unknown regarding the propagation of ultrasound through bone. Because strength and fracture risk are a function of both bone mineral density and architectural structure, this study was carried out to examine how architecture and density interact in ultrasound propagation. Due to the difficulties inherent in obtaining fresh bone specimens and associated architectural and density features, simulation methods were used to explore the interactions of ultrasound with bone. A sample of calcaneal trabecular bone was scanned with micro-CT and subjected to morphological image processing (erosions and dilations) operations to obtain a total of 15 three-dimensional (3-D) data sets. Fifteen two-dimensional (2-D) slices obtained from the 3-D data sets were then analyzed to evaluate their respective architectures and densities. The architecture was characterized through the fabric feature, and the density was represented in terms of the bone volume fraction. Computer simulations of ultrasonic propagation through each of the 15 2-D bone slices were carried out, and the ultrasonic velocity and mean frequency of the received waveforms were evaluated. Results demonstrate that ultrasound propagation is affected by both density and architecture, although there was not a simple linear correlation between the relative degree of structural anisotropy with the ultrasound measurements. This study elucidates further aspects of propagation of ultrasound through bone, and demonstrates as well as the power of computational methods for ultrasound research in general and tissue and bone characterization in particular.

A quantum–mechanical model is proposed to evaluate the bioelectrochemical transduction of low-intensity acoustic exposure, with reference to the binding process of a ligand (messenger) ion to a receptor protein. The interaction of the acoustic exposure with the ligand–receptor chemical reaction is assumed to be mediated by the endogenous electric field of the receptor binding crevice. The displacement of the solvent (water) molecules surrounding the protein, when exposed to the acoustic field, induces the displacement of the receptor molecules from their initial thermal equilibrium position, so that the attractive endogenous force exerted by the receptor on the ligand becomes time-varying at the frequency of the acoustic exposure. A suitable perturbing Hamiltonian operator is evaluated, which transduces the exogenous acoustic exposure into a kind of Stark effect. The density operator method is utilized to statistically evaluate the binding probability in presence of thermal noise. The typical reference intensity (power density) of the incident acoustic wave is 0.1 mW cm −2 in the frequency range 0.5–5 MHz. Usual first-order approximation techniques are employed to evaluate in closed form the change in the binding probability, as compared as usual with its value at thermal equilibrium. By doing so, it is possible to identify a range of parameter values where resonant effects due to the acoustic exposure occur. Thus, a direct numerical integration of the equations is performed in order to validate these first-order findings. The resulting effects are very small, as compared with the binding probability under unperturbed conditions, i.e., at thermal equilibrium, which appears to be the limiting factor of the effectiveness of low-intensity acoustic exposure. These conclusions suggest future research directions, accounting for the out-of-equilibrium living state of a cell and its related basal metabolism, in order to explain those published experimental results which suggest that the binding probability may be significantly affected by a low-intensity exogenous acoustic field.

Power absorption by biological tissues, due to low-intensity electromagnetic exposure at radio frequencies, as those generated by personal telecommunication systems, is typically negligible. Nevertheless, the electromagnetic field is able to affect biological processes, like the binding of a messenger ion to a cell membrane receptor, if some specific conditions occur. The depth of the attracting potential energy well of the binding site must be comparable with the radio frequency photon energy. The dependance of the binding potential energy on the spatial coordinates must be highly non-linear. The ion--receptor system, in absence of the exogenous electromagnetic exposure, must be biased out of thermodynamic equilibrium by the cell basal metabolism. When the above conditions concur a low-intensity radio frequency sinusoidal field is able to induce a steady change of the ion binding probability, which overcomes thermal noise. The model incorporates the effects of both thermal noise and basal metabolism, so that it offers a plausible biophysical basis for potential bioeffects of electromagnetic fields, e.g., those generated by mobile communication systems.

Biological processors of information are shown to be paradigms of Molecular Electronics, suggesting the main features of systems for intelligent information processing at molecular level.

This paper addresses the problem of evaluating theoretically the effects of electromagnetic (EM) exposure on biological systems. EM fields can affect the chemical activity of ions while they interact with the membrane receptors of a cell during a binding process. A coulombic three-state Zeeman model for the binding site is proposed, and the ion adsorption under low-frequency magnetic exposure is described by means of the density operator. The system interactions with the thermal bath are accounted for by a suitable set of lifetime parameters. The limits of a first-order perturbation approach, which allows us to find a closed-form expression for the ion-binding probability, are discussed. The biological effectiveness of a Helmholtz coil exposure system is rather small if computed according to the simplifying assumptions of the paper.

Studies on the effects of low-intensity, low-frequency electromagnetic fields on processes, such as nucleation and precipitation in living matter, have to face rather complex experimental conditions due to the large number of variables to be taken into account. Similar problems are usually associated with many bioelectromagnetic reactions. Inorganic systems where the same phenomena occur are more suitable for investigating the fundamental mechanisms involved. In this paper, we deal with the effect of ELF electromagnetic fields on the nucleation and precipitation of barium oxalate from aqueous solutions of barium nitrate. The effect of ELF electromagnetic fields on nucleation and on crystal growth kinetics lies in the production of fewer nuclei, which grow faster. It is shown that low-intensity ELF fields induce changes in the interfacial energy, which in turn increases both the total apparent free energy of activation for the nucleation process and the subsequent crystal growth kinetics.

The influence of electromagnetic exposure on ligand binding to receptor proteins is a putative early event of the interaction mechanism leading to biological effects. The most recent development of the quantum Zeeman-Stark model is reviewed, addressing the following points: losses due to the collisions of the ligand ion inside the hydrophobic binding crevice and thermal noise; evaluation of the attracting endogenous force of the binding site from the protein data base; out of equilibrium state of the ligand-receptor system due to the basal cell metabolism.

The measurements performed on human subjects by means of radioactive tracers prove the existence of an ergodic linear relationship, which relates the ratio (Co/Mo) of the granulocytes Co in the circulating pool divided by the marginated granulocytes Mo, versus the circulating granulocytes Co. A constraint among the parameters of the granulocyte system, which was previously anticipated on a pure electrochemical basis, is quantitatively evaluated. The ergodicity gives also a constant ratio between the limiting values of the granulocyte margination and demargination rates of different subjects. The latter result suggests that a new electrochemical constraint should exist which expresses the ratio between the maximum rates at which the margination and demargination processes may occur.

Frog erythrocytes dedifferentiate in vitro when exposed to a suitable electromagnetic field in a chemically potentiated microenvironment. These electrochemical stimuli are able to induce a chromatin decondensation, as previously shown by measuring the chromatin accessible sites for acridine orange intercalation by means of flow cytometry (acridine orange green fluorescence). Automated absorption image cytometry of Feulgen stained smeared erythrocytes has been performed to further elucidate the above processes. After measuring or computing the area A of the nucleus, which is related to its volume, the nucleic integrated optical density D, which is related to the DNA content, the average optical density DA = D/A, which is related to chromatin conformation, and the accessible chromatin sites SA = D2/3 A1/3, the following results have been obtained: (a) electromagnetically exposed cells progress to stages which correspond to values of D equal to those of controls, in the potentiating solution, whereas A increases, so that DA is smaller in exposed erythrocytes than in control ones, confirming that chromatin decondensation is occurring as an early dedifferentiation step. (b) By using the electromagnetic signal that is most effective in promoting dedifferentiation, erythrocytes further progress toward more advanced stages, which correspond to larger values of both D and A than in controls, i.e., to larger DNA content. (c) In all cases, the histograms of SA are in agreement with those previously obtained by flow microfluorometry of chromatin conformation (acridine orange green fluorescence). Finally, flow microfluorometric measurements of acridine orange red fluorescence give an increase of RNA content for case (a), as compared with controls, and for case (b) as compared with (a). These results point out that frog erythrocytes can be electromagnetically reactivated, resuming both RNA and DNA syntheses after initial chromatin decondensation.

Automated cytometry has been proposed by us as an extremely sensitive probe of the electrochemical reactivation of quiescent cells, provided that quantitative and specific staining techniques are available for absorption or fluorescence measurements. A complete re-evaluation is given of cell staining by means of the Feulgen reaction for absorption image cytometry, in order to obtain quantitative specificity for DNA amount and chromatin conformation. The possibility of computing from image cytometry the number of chromatin sites accessible to intercalation of small molecules, which should be related to template activity, was previously anticipated by us on an experimental basis, and is now assessed on a theoretical basis, linking together fluorescence flow cytometry and absorption image cytometry. The Feulgen staining technique has been applied to measure the amount of DNA during reactivation of frog erythrocytes and human lymphocytes induced by exposure to electromagnetic (e.m.) fields and by chemical changes of cell environment. Static automated absorption image analysis of Feulgen stained nuclei allows us to evaluate the onset of DNA synthesis and the effectiveness of the electrochemical stimulus on chromatin conformation.

Automated cytometry has been proposed by us as an extremely sensitive probe of cell electrochemical reactivation, provided that quantitative and specific staining techniques are available for fluorescence or absorption measurements. A complete re-evaluation is given of cell staining by means of acridine orange for flow fluorescence cytometry, in order to obtain quantitative specificity for any conformational state of the chromatin DNA and for the amount of RNA. A good agreement is found with experimental data concerning rat thymocytes. The above technique has been applied to measure the structural changes of frog erythrocyte chromatin induced by exposure to electromagnetic fields and by chemical changes of cell environment. Flow automated fluorometry of cell nuclei allows us to evaluate the chromatin changes and the effectiveness of the electrochemical stimulus.

The aggregation between lectins and lymphocyte surface receptors can be affected strongly by a low-level electric field induced in the cell suspension by a time-varying magnetic field. One of the possible mechanisms is the microelectrophoretic effect due to the electric field, which influences the distance (in the mean square sense) between charged ligands and receptors when they are about to separate. On a purely theoretical basis, it is shown that, at low frequencies, an externally induced periodic electric field always decreases the mean lifetime of ligand-receptor complexes. As a consequence, the mitogenic gain obtained by lectin addition to cell suspension is decreased. These results suggest that such a mechanism, if effective, reduces the lectin mitogenic capability and offers a way of handling similar phenomena which have been described for other biological systems.

Cellular morphology changes, which appear related to dedifferentiation (despecialization), have been produced in vitro in the nucleated red blood cell of the frog. This has been achieved by controlled alterations in the electrochemical environment of these living cells, both by a selective modification of the ionic concentrations of an isotonic amphibian Ringer solution, and by the electromagnetic induction of pulsating current having specific waveform parameters. Laser flow microfluorometry shows that the modified Ringer solution is able, per se, to partially trigger the process in the same time interval that certain induced current waveforms can significantly affect the number of cells in the so-called dedifferentiated state. It has also been found that, for a given waveform, the repetition rate appears to have a significant effect on the rate of cell change. Preliminary automated image analysis of cell smears suggests that dedifferentiated and normal cells have the same integrated optical density but different nuclear areas. In conclusion, it appears that, after the initial electrochemical trigger, the early stage of the process, when the cells move from a state of specialized function to one of less specific activity, is the unfolding of their chromatin supercoil, not involving DNA synthesis. Then cytofluorometry allowed us to identify, for the first time, fundamental modifications which occur in the cell nucleus under electromagnetic exposure.

One-dimensional polyelectrolytes are proposed as molecular devices based on soliton propagation. The use of such “molecular wires” as delay lines or shift registers raises the problem of their electrical screening, because, when a large number of these wires are densely packed, cross-talking between them might occur. In order to overcome such a drawback, a detailed study of the polyelectrolyte behavior in an ionic solution has been developed, under equilibrium conditions. The results bring into evidence a condensation process, around each molecular wire, of the mobile ions in the solution. The consequent self-screening effect could be relevant in reducing cross-talking.

A simplified theory of image formation in phase contrast microscopy is presented. It is shown that the phase shift induced in light (related to the refractive index) by the observed object can be reconstructed, point by point, from the phase-contrast digitally sampled image through an appropriate algorithm. This allows one to make quantitative observations on unstained, living cells.