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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.

The statistical properties of the solution of the Langevin–Lorentz equation are analyzed by means of the Fokker–Planck approach. The equation describes the dynamics of an ion that is attracted by a central field and is interacting with a time-varying magnetic field and with the thermal bath. If the endogenous force is assumed to be elastic, then a closed-form expression for the probability density of the process can be obtained, in the case of constant magnetic exposure and, for the time-varying case, at least asymptotically. In the general case, a numerical integration of the resulting set of differential equations with periodically time-varying coefficients has been implemented. A framework for studying the possible effects of low-frequency, low-intensity electromagnetic fields on biological systems has been developed on the basis of the equation. The model assumes that an exogenous electromagnetic field may affect the binding of a messenger attracted by the endogenous force field of its receptor protein. The results are applicable to the analysis of experiments, e.g., exposing a Petri dish, containing a biological sample, to a periodically time-varying magnetic field generated by a pair of Helmholtz coils, most widely used in the scientific literature. The proposed model provides a theoretical mean for evaluating the biological effectiveness of low-frequency, low-intensity electromagnetic exposure.

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.

We describe diffraction effects in ultrasonic group velocity estimation using an insertion technique. We characterize the estimation error produced by diffraction as a function of distance and nominal velocity values. A new method termed Group Velocity Diffraction Correction (GVDC) which corrects for the diffraction effect is presented. Experimental validation of the technique is also presented using measurements made with both 1 MHz and 500 kHz ultrasonic transducer pairs. The results demonstrate that diffraction effects on ultrasonic group velocity estimation are usually small, and may often be neglected. Significant improvement, up to about 50%, in the accuracy of the group velocity estimate can however be obtained using the method described here in those cases in which higher degrees of accuracy are required. >

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.

The possibility of hysteretic behaviours in plane monolayers of electric dipoles is investigated. The basic tool for this study is a model where the electric dipoles can rotate around the nodes of a plane rhombic grid and the electric interactions among dipoles are properly simplified ( Union Jack approximation). In the ideal case of an infinitely extending monolayer, the model yields analytical solutions both for the spatially periodical equilibrium orientations of dipoles and for their stability under the influence of an external electric field. On this basis, a set of hysteresis cycles dealing with different physical situations is obtained and discussed. Then, the much more realistic and complex case of finite-size dipole monolayers is considered and the hysteresis cycles are obtained by computer calculations. The degree of similarity of these numerical results with the analytical ones of the corresponding infinitely extending monolayers puts into evidence the prediction capabilities of such simple model.

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.

This paper attempts to elucidate the mechanism of action of electromagnetic exposure on ligand-receptor binding. The classical Langevin-Lorentz model, which can be used to describe the adsorption process of a messenger ion, is reviewed and discussed. We conclude that low intensity exposure does not affect appreciably the ion dynamics in the presence of background thermal white noise. A more realistic evaluation of the endogenous field present in a binding site leads to a quantum model based on weak Zeeman-Stark effects. The case of the Zeeman effect is studied in detail assuming a three-state binding site. The density operator method is used, introducing suitable lifetimes which model the thermal bath interaction. The closed form expression for the binding probability is found, as a function of the ligand-receptor parameters and of the electromagnetic sinusoidal exposure.

A model based on a simplified form of the electrical interactions among dipoles (closest neighbours- M cellular array M approximation) is used as a basic tool for studying the surface organization properties of dipoles in a planar monolayer. The fundamental equilibrium configurations of such dipoles are obtained under rather general conditions. They are consistent with previous results yielded by a more accurate static model that takes into account long-range interactions. The configuration stabilities and the model accuracy are discussed. We suggest that the proposed short-range cellular array be regarded as the basis for a dynamical model adequate to predicting long-range effects, which are achieved through propagation among neighbours.

In this paper we present the results of an animal bone fracture study which attempts to relate the vibrational response of a healing limb to its mechanical stiffness. Tibial osteotomies are performed on nine rabbits which are sacrificed at different stages of healing. Vibrational measurements are acquired from the healing fractured limb and the contralateral intact limb. The frequency domain vibrational admittance function is estimated using an electromechanical shaker and force and acceleration transducers. A feature known as the energy ratio (ER) derived from the admittance function estimates of both the fractured and intact limbs is used to characterize the strength of the healing fracture relative to the intact value, obtained using a biomechanical torsional test. Results indicate a strong correlation between the ER and relative stiffness of the fractured to intact limb. Vibrational measurements from three human clinical fracture patients over several weeks is also presented. A feedforward neural network scheme is also described for classifying the vibrational data. INTRODUCTION Bone fractures are the most common injury treated by orthopaedic surgeons. Treatment typically consists of immobilization of the fracture site until normal weightbear- ing can resume, i.e., until return of normal stiffness and strength values. Techniques for assessment of bone fracture healing currently consist of radiographic and clinical evalua- tions. Uncertainty regarding the significance of radiological findings may result in unnecessarily long periods of immobiliz- ation. The challenge to develop a reliable bone strength measurement during fracture healing has led several inves- tigators to apply low frequency (50 Hz-2 kHz) vibrational energy techniques (1,21. These previous attempts have not. however, related the vibrational response to healing fractured bone strength, and thus have not achieved any degree of use in orthopaedic practice. The objective of the present study was to develop a vibrational fracture healing assessment method which could overcome limitations of previous approaches, and thus provide orthopedists with a clinical tool for accurate and quantitative strength estimates during fracture healing.

One of the key points for the development of molecular manipulation based technologies is the availability of techniques capable to operate in such a dimensional range. The Scanning Probe Microscopes as well as the Langmuir-Blodgett film deposition technology have always been the best candidates for such a task. In this paper the authors present a method that allows one to obtain controlled surface modifications of cadmium arachidate Langmuir-Blodgett multilayers through Scanning Force Microscopy. Variable depth permanent ablations at the submicron scale have been produced as a function of applied force and scanning speed. In view of an "organic microelectronics technology" this technique can be envisaged as the organic analog of the microelectronics lithographic techniques.

A computer simulation study was carried out on the application of neural networks to a specific electromagnetic (EMF) inverse scattering problem. Small dielectric spheres (radius=1 mm) ranging in relative permittivity from 2 to 100 were individually exposed to a transverse electromagnetic (TEM) plane wave. The spheres' centers were located in the x-y plane, with 0/spl les/x,y/spl les/1 cm. A sensor grid with 25 "point" sensors sampled the EMF scattered by each sphere. The EMF data was evaluated at a frequency of 1 MHz, using a dipole approximation. A principal components analysis was applied to the EMF data to derive a feature vector with 4 components, which were input to a feedforward neural network with one 15 unit hidden layer and 3 outputs, for training. The 3 desired outputs were the x and y coordinates of the sphere center and the relative dielectric permittivity of the sphere, respectively. For an independent EMF (testing) data set, the resulting, root mean-square (RMS) errors were quite small, being 0.03 mm, 0.05 mm, and 1, for the x- and y-sphere center and sphere permittivity estimates, respectively. The results of this study demonstrate the neural networks may be useful in the solution of inverse scattering problems.

This article describes a number of algorithms that are designed to improve both the efficiency and accuracy of finite difference solutions to the Poisson-Boltzmann equation (the FDPB method) and to extend its range of application. The algorithms are incorporated in the DelPhi program. The first algorithm involves an efficient and accurate semianalytical method to map the molecular surface of a molecule onto a three-dimensional lattice. This method constitutes a significant improvement over existing methods in terms of its combination of speed and accuracy. The DelPhi program has also been expanded to allow the definition of geometrical objects such as spheres, cylinders, cones, and parallelepipeds, which can be used to describe a system that may also include a standard atomic level depiction of molecules. Each object can have a different dielectric constant and a different surface or volume charge distribution. The improved definition of the surface leads to increased precision in the numerical solutions of the PB equation that are obtained. A further improvement in the precision of solvation energy calculations is obtained from a procedure that calculates induced surface charges from the FDPB solutions and then uses these charges in the calculation of reaction field energies. The program allows for finite difference grids of large dimension; currently a maximum of 571 3 can be used on molecules containing several thousand atoms and charges. As described elsewhere, DelPhi can also treat mixed salt systems containing mono- and divalent ions and provide electrostatic free energies as defined by the nonlinear PB equation.

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 purpose of this study was to determine the relationship between three-dimensional (3D) trabecular structure and two-dimensional plain radiographic patterns. An in vitro cylinder of human calcaneal trabecular bone was three-dimensionally imaged by micro-CT using synchrotron radiation, at 33.4 micrometer resolution. The original 3D image was processed using 14 distinct sequences of morphologic operations, i.e., of dilations and erosions, to obtain a total of 15 3D models or images of calcaneal trabecular bone. These 15 models had distinct densities (volume fractions) and architectures. The 3D structure of each calcaneal model was assessed using mean intercept length (fabric), by averaging individual fabric measurements associated with each medial-lateral image slice, and determining the relative anisotropy, R(3D), of the structure. A summated pattern or plain radiograph was also computed from the 3D image data for each calcaneal model. Each summated pattern was then locally thresholded, and the resulting two-dimensional (2D) binary image analyzed using the same fabric analysis as used for the 3D data. The anisotropy of the 2D summated pattern was denoted by R(x-ray). The volume fractions of the 15 models ranged from 0.08 to 0.19 with a mean of 0. 14. The medial-lateral anisotropies, R(3D), ranged from 1.38 to 2.54 with a mean of 1.88. The anisotropy of the 2D summated patterns, R(x-ray), ranged from 1.35 to 2.18 with a mean of 1.71. The linear correlation of the 3D trabecular architecture, R(3D), with the radiographic trabecular architecture, R(x-ray), was 0.99 (p0.0001). This study shows that the plain radiograph contains architectural information directly related to the underlying 3D structure. A well-controlled sequential reproducible plain radiograph may prove useful for monitoring changes in trabecular architecture in vivo and in identifying those individuals at increased risk of osteoporotic fracture.

Development of ultrasound nondestructive evaluation techniques (NDT) has involved a combination of both analytic and experimental methods. In contrast, relatively little work has been done on the use of computational methods for experimental design and analysis in NDT. This is due to the relative lack of availability of software for such computations. While computational methods and associated software implementations abound in the electromagnetic and structural analysis engineering communities, no such paradigm exists for ultrasound researchers and engineers. This paper demonstrates a software package, Wave2000, which computes the full solution to the 2D viscoelastic wave equation. 2D objects are represented by graphical images and are comprised of a number of solids and/or liquids. Each material is specified in terms of its material density, the first and second Lame constants, and the first and second viscosities. The program computers the displacement vector was a function of Cartesian coordinates x and y and of time t, and the solution includes effects of diffraction, scattering, reflection, and attenuation of the propagating wave. Wave2000 implements a finite difference solution on a standard personal computer running Microsoft Windows 95 or NT. Sources and receivers may be located anywhere in or on the surface of the object. The source waveform can be practically any temporal function desired, including data collected from an actual transducer, and the receiver data can be sorted in a data file for subsequent processing. Several examples of the use of Wave2000 are given, including simulations of scattering from cracks and propagation through layers of materials and fluid-filled porous structures. Results demonstrate that computational methods can play an important can play an important role in NDT specifically and in ultrasonics in general.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The binding site of most metalloproteins is hydrophobic, so that the ligand metal ion (mass M and charge Q) is attracted by the receptor protein in a dehydrated environment1. Therefore the ion collision frequency can be several order of magnitude lower than in bulk water because the residual water molecules are few2. Furthermore, the protein atoms are slightly displaced by the docking/sailing ion, with respect to their equilibrium positions obtained from the protein data bank. The actual net attracting force is lower than the value calculated on the basis of these fixed atomic positions. Both features are necessary conditions for a ligand-protein system to be susceptible to low-intensity e.m. exposure3. Once the resulting ion potential energy Uend(r) [J] is available versus the ion distance \(\vec r\) [m] from the centre of the binding site, a quantum Zeeman-Stark model of the binding process allows the prediction of its susceptibility to low intensity, e.m. exposure4, i.e., below the current safety standards, at r.f.. A simple and isotropic relationship for Uend(r) [J] has been developed, which can be fitted to the characteristics of the ion-protein system obtained from the protein data bank (fig.1). The binding potential energy depends on four parameters only, i.e. U0 [J], ωend [Hz], ξ [Jm] and R0 [m]. The minimum value of the potential energy at \(\vec r\) = 0 is Uend (0)= -U0. For small values of \(\vec r\) it is Uend ≅-U0 +(1/2)Mω end 2 r2 and, for large values of \(\vec r\), Uend≅-ξ/r, where the order of magnitude of the characteristic distance R0 corresponds to the maximal attracting force (-∇Uend, where ∇ is the nabla operator): $${U_{end}}\left( r \right) = - \xi /r + \left\{ {\xi /r - {U_0} + \xi /{R_0} + \left( {\xi /2R_0^2 - {U_0}/{R_0}} \right)r + \left( {M\omega _{end}^2/2 + \xi /6R_0^3 - {U_0}/2R_0^2} \right){r^2}} \right\}\exp \left( { - r/{R_0}} \right)$$ (1)

The dynamics of the Zn-protoporphyrin IX has been assessed by means of molecular dynamics methods. The conformational rearrangements of the protoporphyrin atoms during the Zn2+ docking (sailing) into (from) the center of its binding site occurs in the picosecond scale, so that any microwave electromagnetic exposure can be considered as almost constant, with respect to the dynamics of the constituent atoms induced by the ion displacement. The computer simulation of the complexation process with and without a low-intensity electromagnetic field has demonstrated the inhibitory effect of the exposure on the complex formation.1 This result has been confirmed experimentally at 2.45 GHz.1,2 We have tested the predictive ability of the quantum Zeeman-Stark (Z-S) model3 of ligand binding against the Zn-protoporphyrin system.

The published experimental results suggest that e.m. exposure (from sub-ELF to RF) at fields or S.A.R. values below the current safety standards, can affect biological processes. Two elementary processes are good candidates to be the first interaction steps: the binding of messenger ions to their receptor proteins and the transport of messenger ions inside protein channels. In both cases the ion dynamics can be often described in terms of the classical Langevin-Lorentz (L-L) model1–4. The closed form integration of the L-L equations under ad hoc simplifying conditions was performed in1–3, for the first time. This rather comprehensive approach includes, as particular cases, all the classical models so far published. In order to analyse or predict the experimental results, the values of the various parameters which enter the L-L equation must be physically plausible, keeping the number of fitting parameters as low as possible. Moreover, their value must be consistent with the effectiveness of the low value of the exposure density. Toward such goals, the following features must be considered. The binding or channel crevice must be hydrophobic, so that it repels the solvent water molecules and strips away the ion hydration shells. If the gradient of the ion endogenous potential energy inside the crevice is an highly non-linear function of the spatial coordinates, the water dipoles can be drifted away from the protein crevice by the resulting endogenous dielectrophoretic force. Therefore, the ion moves in the ballistic Knudsen regime and its Langevin collision frequency can be several order of magnitude lower than in bulk water5. The resulting energy losses are small, so that the ion dynamics become more sensitive to low-intensity e.m. exposure. However, the exogenous signal is typically unable to overcome the Langevin random force (thermal noise) if the ion-protein system, in absence of the e.m. exposure, is at thermal equilibrium. On the other hand, the basal state of any ion-protein systems in a living cell is maintained out of thermal equilibrium by the cell metabolism.

The biological paradigms contributed by cognitive and neurobiological sciences and the physical limits of electronic circuit integration and of information processing define a general framework for any engineering attempt at the emulation of the intelligent performance of the human brain. The emerging picture suggests that intelligent information processing should occur at the molecular level and should use, as single elementary processors, molecules characterized by short-range interactions among close neighboring molecular processors. As an intrinsic character, a molecular array is the physical realization of a cellular automaton and offers the possibility of parallel-processing information at an atomic scale of integration, beyond the anticipated physical limits on circuit integration and on computation. Amphiphilic films obtained in a Langmuir-Blodgett trough and transferred onto a solid hydrophobic substrate are chosen as plausible artificial paradigms, which implement the previous concepts (see Fig.1). A 2-D periodic array of molecular dipoles contacted by suitable electrodes is shown to offer two paramount properties necessary for intelligent processing of information, i.e., non-linearity and memory. A model of the dipolar head interactions on the film plane is formulated and studied. The orientation angle of each dipole component tangential to the film surface is the physical state variable that carries the information parallel - processed by the molecular assembly. In the presence of an exogenous field, the dipole lattice shows a nonlinear behavior based on hysteretic phenomena. Input, output and control electrodes are introduced to explore the possibility of transforming the 2-D dipole array into an elementary molecular processor.

With respect to the study of biological effects due to the exposure of living systems to electromagnetic fields, one of the most widely studied biochemical processes is the binding of light ligands (e.g. metal ions, like Cam) to receptor proteins. Two general models (though simplified to avoid any molecular dynamics simulation) of ion binding emerge from the literature: the classical Langevin-Lorentz (L-L) model and the quantum Zeeman-Stark (Z-S) model.

Organic monolayers of dotriacontane and tetracosanoic acid physisorbed on graphite have been studied by scanning tunneling microscopy at the liquid-solid interface. A high degree of two-dimensional ordering appeared for both the organic compounds observed : the molecules were arranged on graphite in stripelike lamellae of various shape and length. Experimental conditions for high contrast imaging are discussed.

A physical system consisting of a lipid monolayer surrounded by a set of electrodes is defined and proposed as a plausible example of a molecular circuit for information processing. The lipid monolayer is characterized as a cellular array of electric dipoles, where each dipole lying on the monolayer plane represents the head of a lipid molecule. Each dipole experiences the effects of the electric field generated by both the surrounding dipoles and the electrodes. The electrodes’ contribution to the electric field is calculated through a proper discretization of their charge densities. According to this model the dipoles of the cellular array play the role of neurodes whose state is described by the dipole orientations on the plane, and a cellular automation can be defined once the orientation values have been properly discretized. The electrodes act as input‐ and output‐signal sources. it is shown that the simple system considered here, i.e., a two‐port system, is characterized by a nonlinear voltage tran...

Type I Gaucher disease is a genetic disorder afflicting between 5000 and 10,000 Ashkenazi Jews in the United States. It is characterized by the deficient activity of the lysosomal hydrolase, acid s-glucosidase. The progressive infiltration and replacement of the bone marrow by “Gaucher cells” (lipid-filled macrophages) lead sequentially to diffuse osteopenia, localized destruction, ischemic necrosis, and osteosclerosis. Degenerative changes in the skeleton are the leading cause of disability in patients with type I disease, and some degree of osteopenia and osteolysis occurs in virtually all patients. However, the extent of bone disease also is markedly variable, which makes it very difficult to predict the course of the disease once a diagnosis has been made.

The paper deals with a study of the spatially periodical dipole patterns that result from the interactions among polar lipid heads, whose tails are confined to a planar thin layer. The model is based on a continuous approach that assumes the dipole layer to be a planar region of infinitesimal thickness; according to this approach the dipole distributions are first represented through proper continuous functions, which are a normal dipole vector per unit area and a given surface charge density. Both of them must be periodical with respect to the coordinates of the plane, as they must be compatible with the periodic electric field configurations studied in this paper. It is shown that the periodical patterns associated to discrete dipoles can be derived from the afore-side continuous representation through the definition of “elementary cells” that contain a finite number of “subdomains” each of which corresponds to a single lipid molecule. A set of dipole patterns is obtained and discussed for the case of a square elementary cell. Results point out that both ferroelectric and antiferroelectric organizations of the dipole components on the layer plane do exist.

Non-invasive therapeutic treatment of bone in vivo using ultrasound in conjunction with application of a biochemical compound or bone growth factor is performed by subjecting bone to an ultrasound signal supplied to an ultrasound transducer placed on the skin of a bony member, and involving a repetitive finite duration signal consisting of plural frequencies that are in the ultrasonic range to 20 MHz. Concurrent with application of the ultrasound is the utilization of a bone growth factor applied to the skin of a bony member before stimulation with ultrasound. Ultrasonic stimulation is operative to transport the bone growth factor to the bone and then to synergistically enhance the interaction of the bone growth factor with the bone, whereby to induce healing, growth and ingrowth responses. In another embodiment, a vibrational or mechanical input together with a biochemical compound enhances both bone fracture healing and treats osteoporosis.

Non-invasive therapeutic treatment and/or quantitative evaluation of musculoskeletal tissue are performed in vivo by subjecting musculoskeletal tissue (11) to an ultrasonic acoustic signal pulse excitation, involving a composite sine wave signal consisting of plural discrete frequencies that are spaced in the ultrasonic region to approximately 2 MHZ, and repeated substantially in the range of 1 Hz to 1000 Hz. In a quantitative evaluation, the signal is supplied to one of two transducers (12, 13) on opposite sides of the tissue, and the signal received by the other transducer is processed (14): (a) to obtain an averaged per-pulse signal, and (b) to produce a Fourier transform of the averaged per-pulse tissue transmittal signal. In a separate operation, the same transducers are subjected to the same excitation, reception and processing, using a medium of known acoustic properties and path length to produce a reference Fourier transform. In a therapeutic treatment, the transducer (12) excited by the composite sine wave signal, is applied for a time period and magnitude.

A review of the evolution of electronic information processing from small-scale integration to ultra-large-scale integration and beyond is presented recalling the milestones achieved in the development of electronic hardware. Physical principles which limit the size and performances of electronic circuits and the rate of information processing are discussed. In order to explore the new courses offered by organic molecular materials towards atomic-scale integration, the elementary computational capabilities of molecules are discussed by casting the quantum dynamic equations in the framework of system theory. Bond dynamics in polymeric networks is considered, thus showing the possibility of obtaining molecular probabilistic circuits.

The average behaviour of dipoles (water molecules) in the binding regions of charged ligands, where the local electric field may be high and nonuniform, is investigated. The model incorporates all the features of Clausius-Mossotti's, Debye's, Onsager's, and Kirkwood's approaches and assumes, as a novel feature, that the dielectrophoretic drift of dipoles is balanced by dipole diffusion. Our analysis shows that the current view of bound water near charged surfaces should be re-examined. A new relationship among local permittivity, electric field, and water density is found that could explain why water molecules are rejected by charged molecular crevices which can engineer ligand binding at very high rates as compared to bulk water.

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.

The behaviour of electric dipoles (water molecules) under the action of a high and nonuniform electric field is investigated. The model incorporates all the features of Clausius-Mossotti’s Debye’s, Onsager’s and Kirkwood’s approaches, and assumes, as a novel feature, that the dielectrophoretic drift of dipoles is balanced by dipole diffusion. A new relationship among local permittivity, electric field and water density is found that could explain why water molecules are rejected by charged molecular crevices which can engineer the binding of ionized ligands at very high rates as compared to bulk water.

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.

The first-order nonlinear analysis of IMPATT diodes is performed and a model is obtained in which the nonlinear effects due to avalanche are separated from the activity and transit-time effects. Such a mildly nonlinear model is suitable for CAD applications. The determination of the model parameters by means of small signal measurements is outlined, and the applicability of the proposed model is demonstrated on real devices.

The motion of ions in aqueous environments under the action of electric fields is considered and the effect of superimposed ac and dc magnetic fields is investigated. The model adopted is likely to apply for exogenous signals in a frequency range 0 to 10 MHz, ac electric fields smaller than 10 V/m, and magnetic inductions smaller than 10−2 T. The paper shows how small values of the viscosity, which can occur near macromolecular surfaces, are necessary to obtain an appreciable field effect. Some effects of the magnetic exposure are discussed, which are relevant to 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.

The possibility of controlling the activity of biological processes by means of an electromagnetic (em) field is well established in the literature, and already leads to clinical applications (1).