Thirty-five years in bioelectromagnetics research

For 35 years, I have been involved in various bioelectromagnetics research projects including acute and long-term radiofrequency (RF) bioeffects studies, dosimetry, exposure systems, MRI safety, cancer studies involving hyperthermia and electrochemical treatment, development of RF exposure and measurement standards, and product compliance. My first study demonstrated that effects on isolated nerve and muscle preparations were due to thermal effects of RF exposure. The recording of cochlear microphonics in animals shows the mechanical nature of the microwave auditory effect. In 1992, we published the results of a large-scale lifetime study in which 100 rats were sham-exposed and 100 rats were exposed for 21 h/day for 25 months to a pulsed RF signal. In dosimetry studies, human models were employed as well as many animal species including mice, rats, rabbits, monkeys, and birds of many sizes. Cancer hyperthermia studies demonstrated that knowledge of temperature distribution was crucial for successful treatment. Research on electrochemical treatment of tumors with direct current involved cellular, animal, and clinical studies. Over the past few decades, there has been rather extensive investigation of the public health impact of RF exposure. In my opinion, future research in bioelectromagnetics should place greater emphasis on medical applications.     

Electric and magnetic fields in cryopreservation: A response

Our recent studies showed that a programmed freezer with a magnetic field (CAS freezer) is helpful in the survival of periodontal ligament (PDL) cells after cryopreservation. The theory is that a magnetic field can prevent the cluster from growing by causing it to vibrate. In this letter, we commented in detail on the influence of a magnetic field during cryopreservation.     

Experimental study and mechanism analysis on bioeffects by nanosecond electromagnetic pulses

The athermal bioeffects caused by nanosecond electromagnetic pulses with body cells was studied by using a broad band transverse EM-wave cell (BTEM CELL). The experimental system and preliminary mechanism analysis were presented.     

Catalytic mechanisms for phosphotriesterases

Phosphotriesters are one class of highly toxic synthetic compounds known as organophosphates. Wide spread usage of organophosphates as insecticides as well as nerve agents has lead to numerous efforts to identify enzymes capable of detoxifying them. A wide array of enzymes has been found to have phosphotriesterase activity including phosphotriesterase (PTE), methyl parathion hydrolase (MPH), organophosphorus acid anhydrolase (OPAA), diisopropylfluorophosphatase (DFP), and paraoxonase 1 (PON1). These enzymes differ widely in protein sequence and three-dimensional structure, as well as in catalytic mechanism, but they also share several common features. All of the enzymes identified as phosphotriesterases are metal-dependent hydrolases that contain a hydrophobic active site with three discrete binding pockets to accommodate the substrate ester groups. Activation of the substrate phosphorus center is achieved by a direct interaction between the phosphoryl oxygen and a divalent metal in the active site. The mechanistic details of the hydrolytic reaction differ among the various enzymes with both direct attack of a hydroxide as well as covalent catalysis being found. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.     

Electromagnetic dosimetry in a sitting rhesus model at 225 MHz

Dosimetric measurements in a 9.5-kg tissue-equivalent rhesus model were conducted at 225 MHz using a nonperturbing temperature probe and a gradient-layer calorimeter. Temperature probe measurements showed deep penetration of electromagnetic energy, and calorimeter experiments showed an average SAR (0.285 W/kg per mW/cm²) that was nearly three times greater than that observed for the same model at 1.29 GHz.     

The mutation buffering concept of biomolecular structure

Redundant elements in proteins and nucleic acids serve to buffer the effect of point mutations on features of conformation critical for function. Mutation buffering associated with mechanistically redundant amino acids facilitates the evolution of proteins. Such redundant amino acids accumulate by hitch-hiking along with the evolutionary advances which they facilitate. Redundancies in DNA (such as introns and repetitive DNA) prevent extraneous sequence dependent conformational effects from interfering with readout. They also facilitate regulatory evolution. According to the mutation buffering concept biological organizations are selected to facilitate evolution. As a consequence biological information processing is very different from information processing in man-made computers. The link between molecular conformation, evolutionary processes, and information processing is formulated in terms of a tradeoff principle. By utilizing mutation buffering biological systems sacrifice programmability; by achieving programmability digital computers make mutation buffering computationally expensive and hence sacrifice evolutionary adaptability.     

农业激光生物效应的可比性实验与数理统计

本文根据数理统计的原理和方法,初步讨论了农业激光生物效应可比性实验的问题。     

FRET and optical trapping reveal mechanisms of actin activation of the power stroke and phosphate release in myosin V

Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.     

Sirtuin chemical mechanisms

Sirtuins are ancient proteins widely distributed in all lifeforms of earth. These proteins are universally able to bind NAD⁺, and activate it to effect ADP-ribosylation of cellular nucleophiles. The most commonly observed sirtuin reaction is the ADP-ribosylation of acetyllysine, which leads to NAD⁺-dependent deacetylation. Other types of ADP-ribosylation have also been observed, including protein ADP-ribosylation, NAD⁺ solvolysis and ADP-ribosyltransfer to 5,6-dimethylbenzimidazole, a reaction involved in eubacterial cobalamin biosynthesis. This review broadly surveys the chemistries and chemical mechanisms of these enzymes.     

The vacuolar potential of characean cells subjected to electromagnetic radiation in the range 200–8,200 MHz

Single giant cells of Chara braunii and Nitella flexilis were placed in a microstrip exposure apparatus and subjected to bursts of electromagnetic radiation (carrier frequencies from 200 to 8,200 MHz) at a nominal power level of 100 W/m². The vacuolar potential was monitored with a micropipette, and offsets as low as 1 μ V could be resolved in real time by suitable filtering and signal averaging; under these conditions, no offsets of the vacuolar potential were detected. At much higher power levels (corresponding to > 2 V rms between microstrip and ground plane), the slow hyperpolarizing ramp reported at lower frequencies could be seen but, because of insufficient power, could not be accurately measured. It appeared to decay beyond 500 MHz and to be absent at and above 950 MHz. To investigate reports that snail neurons irradiated for 1 h at 2,450 MHz and approximately 15.5 W/kg developed lowered membrane resistivities, Characean cells were exposed in the microstrip apparatus for 1 h at 2,450 MHz and 230 W/m²; their membrane resistivities were found to be lowered about 18.5%.     

The IAEA Radiotracer Biodistribution Template – A community resource for supporting the standardization and reporting of radionuclide pre-dosimetry data

Radionuclide absorbed-dose dosimetry is an active area of development and has the potential to positively impact molecular radiotherapies. At present, many of the operations required to perform dosimetry calculations are unstandardized and unestablished. While the current methodology allows reasonable dosimetry estimates to be derived and published, it can be difficult to understand, and reproduce, each others’ work. To help alleviate this we have identified the collection of biodistribution information as a key step in all internal dosimetry calculations, and present a template that can be used to standardize its documentation and reporting.A generalized biodistribution template entitled the IAEA Radiotracer Biodistribution Template (IAEA RaBiT) has been built and distributed for users performing biodistribution measurements in the community. The template enables robust recording of dosimetry-relevant information through standardization of details and their format. It has been designed to be simple and easy to use, and establish a structured recording of a common reference point in dosimetry operations – biodistribution data documentation. Improved documentation procedures may benefit organization of in house data, or be used to disseminate details throughout the community – for example to supplement dosimetry related publications. The standard format information may also enable the creation of new dosimetry related tools and protocols and support robust population databases.As dosimetry in nuclear medicine becomes more routinely applied in clinical applications, we need to develop the infrastructure for robustly handling large amounts of these data. Our IAEA RaBiT can be used as a standard format structure for data collection, organization, and dissemination.     

Far-field microwave dosimetry in a rhesus monkey model

Dosimetric measurements were made in a muscle-equivalent model of an adult rhesus monkey subjected to far-field irradiation at 1.29 GHz. Profiles of microwave-induced heating in the model were obtained at eight locations, and a gradient-layer whole-body calorimeter was used to measure total absorbed energy. Average specific absorption rate (SAR) was calculated both from the calorimeter experiments and from the local temperature measurements. Thermographic imaging techniques were used to qualitatively show the microwave-induced surface heating patterns. For this model the calculated average SAR was 0.155 (W/kg)/(mW/cm²) which, at 1.29 GHs, makes the absorption cross section 84% of the geometric shadow cross section. The SAR is about three times that predicted for a prolate spheroidal model of similar mass. A disproportionally high absorption occured in the legs of the model positioned parallel to the E-polarization because of what is believed to be partial-body resonance.     

What are non-thermal electric biological effects?

A discussion of the general implication of the existance of non-thermal biological effects of electromagnetic fields is presented.     

DNA mechanics and its biological impact

Almost all nucleoprotein interactions and DNA manipulation events involve mechanical deformations of DNA. Extraordinary progresses in single-molecule, structural, and computational methods have characterized the average mechanical properties of DNA, such as bendability and torsional rigidity, in high resolution. Further, the advent of sequencing technology has permitted measuring, in high-throughput, how such mechanical properties vary with sequence and epigenetic modifications along genomes. We review these recent technological advancements, and discuss how they have contributed to the emerging idea that variations in the mechanical properties of DNA play a fundamental role in regulating, genome-wide, diverse processes involved in chromatin organization.     

Effects of a 30 kV/m, 60 Hz electric field on the social behavior of baboons: a crossover experiment.

Using a crossover experimental design, we evaluated our earlier findings that exposure to a 30 kV/m, 60 Hz electric field for 12 hours per day, 7 days per week for 6 weeks produced significant changes in the performance rates of social behaviors among young adult male baboons. In the crossover experiment, the former control group was exposed to a 30 kV/m, 60 Hz electric field for 3 weeks. Only an extremely small, incidental magnetic field was generated by the exposure apparatus. We found that electric-field exposure again produced increases in the performance rates that index Passive Affinity, Tension, and Stereotypy. These findings, combined with results from our other electric-field experiments, indicate that exposure to strong electric fields, in the absence of associated magnetic fields, consistently produces effects that are expressed as increases in rates of performance of social behaviors in young adult male baboons.     

Search for frequency-specific effects of millimeter-wave radiation on isolated nerve function

Effects of a short-term exposure to millimeter waves (CW, 40–52 GHz, 0.24–3.0 mW/cm²) on the compound action potential (CAP) conduction were studied in an isolated frog sciatic nerve preparation. CAPs were evoked by either a low-rate or a high-rate electrical stimulation of the nerve (4 and 20 paired pulses/s, respectively). The low-rate stimulation did not alter the functional state of the nerve, and the amplitude, latency, and peak latency of CAPs could stay virtually stable for hours. Microwave irradiation for 10–60 min at 0.24–1.5 mW/cm², either at various constant frequencies or with a stepwise frequency change (0.1 or 0.01 GHz/min), did not cause any detectable changes in CAP conduction or nerve refractoriness. The effect observed under irradiation at a higher field intensity of 2–3 mW/cm² was a subtle and transient reduction of CAP latency and peak latency along with a rise of the test CAP amplitude. These changes could be evoked by any tested frequency of the radiation; they reversed shortly after cessation of exposure and were both qualitatively and quantitatively similar to the effect of conventional heating of 0.3–0.4°C. The high-rate electrical stimulation caused gradual and reversible decrease of the amplitude of conditioning and test CAPs and increased their latencies and peak latencies. These changes were essentially the same with and without irradiation (2.0–2.7 or 0.24–0.28 mW/cm²), except for attenuation of the decrease of the test CAP amplitude. This effect was observed at both field intensities, but was statistically significant only for certain frequencies of the radiation. Within the studied limits, this effect appeared to be dependent on the frequency rather than on the intensity of the radiation, but this observation requires additional experimental confirmation. Bioelectromagnetics 18:324–334, 1997. © 1997 Wiley-Liss, Inc.     

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm². A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm². The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm². The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm². Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm² were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm² and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.