Spectroscopy of excised skin patches exposed to THz and far-IR radiation.

Applications of far infrared (Far-IR) and terahertz (THz) radiation in areas such as healthcare and security are fast-growing. As a consequence, humans and the environment are becoming more exposed to mm-wave and Far-IR radiation than previously. We examined typical skin-care and sunscreen ingredients and propitiatory products with transmission FTIR, ATR-FTIR and THz-time domain spectroscopy (THz-TDS) methods using fresh and dehydrated toad and fresh human skin samples for their absorption properties in these frequency ranges. The skin hydration compounds glycerol and sorbitol have comparable absorption characteristics to physiological bulk water. Products containing these and similar hydrating compounds have significant Far-IR absorption characteristics. The sunscreen ingredients ZnO (20 micron), TiO2 (mesh 325), and graphene platelet demonstrate a generally poor Far-IR absorbance, with TiO2 displaying some frequency-specific absorption in the 3-6 THz and 12 THz regions. The Far-IR absorbance of proprietary sunscreens was, however, shown not to be significant. The absorption properties of melanin, collagen, bound water, and other constituents are significant in dehydrated skin samples but are not of the same order of importance as the hydrating agents examined.

Computer simulation study of the penetration of pulsed 30, 60 and 90 GHz radiation into the human ear.

There is increasing interest in applications which use the 30 to 90 GHz frequency range, including automotive radar, 5 G cellular networks and wireless local area links. This study investigated pulsed 30-90 GHz radiation penetration into the human ear canal and tympanic membrane using computational phantoms. Modelling involved 100 ps and 20 ps pulsed excitation at three angles: direct (orthogonal), 30° anterior, and 45° superior to the ear canal. The incident power flux density (PD) estimation was normalised to the International Commission on Non-Ionizing Radiation Protection (1998) standard for general population exposure of 10 Wm-2 and occupational exposure of 50 Wm-2. The PD, specific absorption rate (SAR) and temperature rise within the tympanic membrane was highly dependent on the incident angle of the radiation and frequency. Using a 30 GHz pulse directed orthogonally into the ear canal, the PD in the tympanic membrane was 0.2% of the original maximal signal intensity. The corresponding PD at 90 GHz was 13.8%. A temperature rise of 0.032° C (+20%, -50%) was noted within the tympanic membrane using the equivalent of an occupational standard exposure at 90 GHz. The central area of the tympanic membrane is exposed in a preferential way and local effects on small regions cannot be excluded. The authors strongly advocate further research into the effects of radiation above 60 GHz on the structures of the ear to assist the process of setting standards.

Computational absorption and reflection studies of normal human skin at 0.45 THz.

Applications using terahertz (THz) frequency radiation will inevitably lead to increased human exposure. The power density and specific absorption rate (SAR) simulations of thin skin at 0.45 THz show the bulk of the energy being absorbed in the upper stratum spinosum, and the maximal temperature rise is in the lower stratum spinosum. There are regions of SAR increase of 100% above the local average at the stratum spinosum/stratum basale boundary. The dead Stratum Corneum layer protects underlying tissues in thick skin. Reflection studies suggest that acute angles and the use of polarised incident radiation may enhance the assessment of diabetic neuropathy.

Computational simulations of the penetration of 0.30 THz radiation into the human ear.

There is an increasing interest in industrial and security applications and the establishment of wireless communication operating at frequencies of up to 0.30 THz. Soft tissue has a high coefficient of absorption at 0.30 THz and this limits effective penetration of the energy to a depth of 0.2 to 0.4 mm. The capacity of 0.30 THz radiation to access the deeper parts of the ear by diffusing through the ear canal and exposing the tympanic membrane (ear drum) to the radiation has not been studied. Simulations show that, with excitation parallel to the ear canal, the average power flux density within the central tympanic membrane region is 97% of the incident excitation. The structures of the outer ear are highly protective; less than 0.4% of the power flux density is directed at 45° from the parallel reached the same region. Given the sensitivity of the tympanic membrane to mechanical change, in-vivo assessment of the penetration of 0.3 THz into the ear canal is warranted to assess the suitability of the present radiation safety limits and to inform 0.3 THz emitting device deign.

Computational phantom study of frozen melanoma imaging at 0.45 terahertz.

Terahertz radiation (THz) is highly absorbed by liquid water. This creates the possibility of medical imaging on the basis of the water content difference between normal and diseased tissue. The effective penetration of THz is limited, however, to a tissue depth of 0.2-0.3 mm at body temperature. A unique feature of the 0.1-2.0 THz frequency is that there is a high disparity between liquid water absorption and ice absorption, with ice being 100 times more permeable to the radiation than liquid water. This results in 90% of the radiation surviving to 1.0 mm in ice, permitting the imaging of frozen tissues to a depth of 5.0 mm. This method is practical as an in vivo procedure before or during surgical excision. Finite difference time domain (FDTD) computational modeling of frozen normal skin and frozen melanoma was undertaken using tissue phantoms. The study suggests that sufficient contrast exists to differentiate normal frozen skin and melanoma on the basis of the difference of water content alone. When the melanin pigment in melanomas is modeled as a significant absorber of THz, the contrast changes. Based on the modeling, further exploration of the "THz-skin freeze" imaging technique is justified. In the modeling, the boundary between the frozen tissue and non-frozen tissue is shown to be strongly reflective. If the reflective properties of the boundary are substantiated, the "THz-skin freeze" technique will have applications in other areas of skin diagnostics and therapeutics. Bioelectromagnetics. 40:118-127, 2019. © 2019 Bioelectromagnetics Society.

The architecture of EGFR's basal complexes reveals autoinhibition mechanisms in dimers and oligomers.

Our current understanding of epidermal growth factor receptor (EGFR) autoinhibition is based on X-ray structural data of monomer and dimer receptor fragments and does not explain how mutations achieve ligand-independent phosphorylation. Using a repertoire of imaging technologies and simulations we reveal an extracellular head-to-head interaction through which ligand-free receptor polymer chains of various lengths assemble. The architecture of the head-to-head interaction prevents kinase-mediated dimerisation. The latter, afforded by mutation or intracellular treatments, splits the autoinhibited head-to-head polymers to form stalk-to-stalk flexible non-extended dimers structurally coupled across the plasma membrane to active asymmetric tyrosine kinase dimers, and extended dimers coupled to inactive symmetric kinase dimers. Contrary to the previously proposed main autoinhibitory function of the inactive symmetric kinase dimer, our data suggest that only dysregulated species bear populations of symmetric and asymmetric kinase dimers that coexist in equilibrium at the plasma membrane under the modulation of the C-terminal domain.

Effect of adverse environmental conditions and protective clothing on temperature rise in a human body exposed to radiofrequency electromagnetic fields.

This study considers the computationally determined thermal profile of a finely discretized, heterogeneous human body model, simulating a radiofrequency electromagnetic field (RF-EMF) worker wearing protective clothing subject to RF-EMF exposure, and subject to various environmental conditions including high ambient temperature and high humidity, with full thermoregulatory mechanisms in place. How the human body responds in various scenarios was investigated, and the information was used to consider safety limits in current international RF-EMF safety guidelines and standards. It was found that different environmental conditions had minimal impact on the magnitude of the thermal response due to RF-EMF exposure, and that the current safety factor of 10 applied in international RF-EMF safety guidelines and standards for RF-EMF workers is generally conservative, though it is only narrowly so when workers are subjected to the most adverse environmental conditions. Bioelectromagnetics. 38:356-363, 2017. © 2017 Wiley Periodicals, Inc.

Imaging Cellular Dynamics with Spectral Relaxation Imaging Microscopy: Distinct Spectral Dynamics in Golgi Membranes of Living Cells.

Spectral relaxation from fluorescent probes is a useful technique for determining the dynamics of condensed phases. To this end, we have developed a method based on wide-field spectral fluorescence lifetime imaging microscopy to extract spectral relaxation correlation times of fluorescent probes in living cells. We show that measurement of the phase and modulation of fluorescence from two wavelengths permit the identification and determination of excited state lifetimes and spectral relaxation correlation times at a single modulation frequency. For NBD fluorescence in glycerol/water mixtures, the spectral relaxation correlation time determined by our approach exhibited good agreement with published dielectric relaxation measurements. We applied this method to determine the spectral relaxation dynamics in membranes of living cells. Measurements of the Golgi-specific C6-NBD-ceramide probe in living HeLa cells revealed sub-nanosecond spectral dynamics in the intracellular Golgi membrane and slower nanosecond spectral dynamics in the extracellular plasma membrane. We interpret the distinct spectral dynamics as a result of structural plasticity of the Golgi membrane relative to more rigid plasma membranes. To the best of our knowledge, these results constitute one of the first measurements of Golgi rotational dynamics.

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms.

Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling.

Bioelectromagnetics Research within an Australian Context: The Australian Centre for Electromagnetic Bioeffects Research (ACEBR).

Mobile phone subscriptions continue to increase across the world, with the electromagnetic fields (EMF) emitted by these devices, as well as by related technologies such as Wi-Fi and smart meters, now ubiquitous. This increase in use and consequent exposure to mobile communication (MC)-related EMF has led to concern about possible health effects that could arise from this exposure. Although much research has been conducted since the introduction of these technologies, uncertainty about the impact on health remains. The Australian Centre for Electromagnetic Bioeffects Research (ACEBR) is a National Health and Medical Research Council Centre of Research Excellence that is undertaking research addressing the most important aspects of the MC-EMF health debate, with a strong focus on mechanisms, neurodegenerative diseases, cancer, and exposure dosimetry. This research takes as its starting point the current scientific status quo, but also addresses the adequacy of the evidence for the status quo. Risk communication research complements the above, and aims to ensure that whatever is found, it is communicated effectively and appropriately. This paper provides a summary of this ACEBR research (both completed and ongoing), and discusses the rationale for conducting it in light of the prevailing science.

Estimation of dielectric values for tissue water in the Terahertz range.

As the availability of Terahertz (THz) sources and their application expands, interaction with biological material needs to be well-understood. In order to accurately estimate the energy absorption pattern in skin and other tissues in the THz and far Infrared regions, values of dielectric parameters ϵ and σ are required. We present an approach for tissue water, which uses literature values of complex refractive index for pure water together with some considerations regarding the effects of dissolved salts. The approach also involves modeling of Debye and Lorentz absorption parameters, which provides a method for the estimation of ϵ and σ in other tissues. Bioelectromagnetics. 37:563-567, 2016. © 2016 Wiley Periodicals, Inc.

Lessons and Perspectives from a 25-Year Bioelectromagnetics Research Program.

The question of whether electromagnetic fields from electric power or telecommunications systems can be linked unequivocally to health detriments has occupied scientific research endeavors for nearly half a century. For 25 years, the bioelectromagnetic research group at Swinburne University in Melbourne, Australia, has pursued a series of investigations with relevant endpoints, such as neurophysiological and neuropsychological effects, cell calcium level changes, proliferation, and genotoxic effects. Most have shown no significant changes due to fields, however, in some pilot studies significant changes were revealed, but in most cases these were not replicated in follow-up studies. This highlights a feature of this research area, generally; the unambiguous identification of small changes in noisy data where the understanding of possible interaction mechanisms is lacking. On the other hand, mathematical modelling studies, particularly with respect to fields near metallic implants, in workers exposed to fields in harsh environmental conditions and at very high frequencies (THz), continue to add to the expanding knowledge database on the characteristics of the complex electromagnetic environment we live in today.

Ultra-pure, water-dispersed Au nanoparticles produced by femtosecond laser ablation and fragmentation.

Aqueous solutions of ultra-pure gold nanoparticles have been prepared by methods of femtosecond laser ablation from a solid target and fragmentation from already formed colloids. Despite the absence of protecting ligands, the solutions could be (1) fairly stable and poly size-dispersed; or (2) very stable and monodispersed, for the two fabrication modalities, respectively. Fluorescence quenching behavior and its intricacies were revealed by fluorescence lifetime imaging microscopy in rhodamine 6G water solution. We show that surface-enhanced Raman scattering of rhodamine 6G on gold nanoparticles can be detected with high fidelity down to micromolar concentrations using the nanoparticles. Application potential of pure gold nanoparticles with polydispersed and nearly monodispersed size distributions are discussed.

The effect of translational motion on FLIM measurements-single particle phasor-FLIM.

Fluorescence lifetime imaging microscopy or FLIM provides a versatile tool for spatially-mapping macromolecular interactions and environments through pixel-by-pixel resolution of the excited-state lifetime. In conventional frequency-domain FLIM the phase and modulation of the detected fluorescence are determined by the photophysics of the fluorophore only. However, translational motion on the timescale of FLIM acquisition can significantly perturb apparent phase and modulation values owing to intensity fluctuations and phase decoherence. Using the phasor plot we outline a simple analytic theory, numerical simulations and measurements on fluorescent beads (ex 470 nm, em 520 nm). Fluctuations due to particle motions result in an increase in the number and spread of phasors, an effect we refer to as phasor broadening. The approach paves the way for the measurement of lifetimes and translational motion from one experiment.