Search

Objective. Optogenetic stimulation of the auditory nerve offers the ability to overcome the limitations of cochlear implants through spatially precise stimulation, but cannot achieve the temporal precision nor temporal fidelity required for good hearing outcomes. Auditory midbrain recordings have indicated a combined (hybrid) stimulation approach may permit improvements in the temporal precision without sacrificing spatial precision by facilitating electrical activation thresholds. However, previous research has been conducted in undeafened or acutely deafened animal models, and the impact of chronic deafness remains unclear. Our study aims to compare the temporal precision of auditory nerve responses to optogenetic, electrical, and combined stimulation in acutely and chronically deafened animals. Methods. We directly compare the temporal fidelity (measured as percentage of elicited responses) and precision (i.e. stability of response size and timing) of electrical, optogenetic, and hybrid stimulation (varying sub-threshold or supra-threshold optogenetic power levels combined with electrical stimuli) through compound action potential and single-unit recordings of the auditory nerve in transgenic mice expressing the opsin ChR2-H134R in auditory neurons. Recordings were conducted immediately or 2–3 weeks following aminoglycoside deafening when there was evidence of auditory nerve degeneration. Main results. Results showed that responses to electrical stimulation had significantly greater temporal precision than optogenetic stimulation (p < 0.001 for measures of response size and timing). This temporal precision could be maintained with hybrid stimulation, but only when the optogenetic stimulation power used was below or near activation threshold and worsened with increasing optical power. Chronically deafened mice showed poorer facilitation of electrical activation thresholds with concurrent optogenetic stimulation than acutely deafened mice. Additionally, responses in chronically deafened mice showed poorer temporal fidelity, but improved temporal precision to optogenetic and hybrid stimulation compared to acutely deafened mice. Significance. These findings show that the improvement to temporal fidelity and temporal precision provided by a hybrid stimulation paradigm can also be achieved in chronically deafened animals, albeit at higher levels of concurrent optogenetic stimulation levels.

Antibiotic resistance is a growing concern that is driving the exploration of alternative ways of killing bacteria. Here we show that gold nanoparticles synthesized by the mycelium of Mucor plumbeus are an effective medium for antimicrobial photodynamic therapy (PDT). These particles are spherical in shape, uniformly distributed without any significant agglomeration, and show a single plasmon band at 522&ndash, 523 nm. The nanoparticle sizes range from 13 to 25 nm, and possess an average size of 17 &plusmn, 4 nm. In PDT, light (from a source consisting of nine LEDs with a peak wavelength of 640 nm and FWMH 20 nm arranged in a 3 &times, 3 array), a photosensitiser (methylene blue), and oxygen are used to kill undesired cells. We show that the biogenic nanoparticles enhance the effectiveness of the photosensitiser, methylene blue, and so can be used to kill both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The enhanced effectiveness means that we could kill these bacteria with a simple, small LED-based light source. We show that the biogenic gold nanoparticles prevent fast photobleaching, thereby enhancing the photoactivity of the methylene blue (MB) molecules and their bactericidal effect.

Optical stimulation is a paradigm-shifting approach to modulating neural activity that has the potential to overcome the issue of current spread that occurs with electrical stimulation by providing focused stimuli. But optical stimulation either requires high power infrared light or genetic modification of neurons to make them responsive to lower power visible light. This work examines optical activation of auditory neurons following optogenetic modification via AAV injection in two species (mouse and guinea pig). An Anc80 viral vector was used to express the channelrhodopsin variant ChR2-H134R fused to a fluorescent reporter gene under the control of the human synapsin-1 promoter. The AAV was administered directly to the cochlea (n = 33) or posterior semi-circular canal of C57BL/6 mice (n = 4) or to guinea pig cochleae (n = 6). Light (488 nm), electrical stimuli or the combination of these (hybrid stimulation) was delivered to the cochlea via a laser-coupled optical fibre and co-located platinum wire. Activation thresholds, spread of activation and stimulus interactions were obtained from multi-unit recordings from the central nucleus of the inferior colliculus of injected mice, as well as ChR2-H134R transgenic mice (n = 4). Expression of ChR2-H134R was examined by histology. In the mouse, transduction of auditory neurons by the Anc80 viral vector was most successful when injected at a neonatal age with up to 89% of neurons transduced. Auditory neuron transductions were not successful in guinea pigs. Inferior colliculus responses to optical stimuli were detected in a cochleotopic manner in all mice with ChR2-H134R expression. There was a significant correlation between lower activation thresholds in mice and higher proportions of transduced neurons. There was no difference in spread of activation between optical stimulation and electrical stimulation provided by the light/electrical delivery system used here (optical fibre with bonded 25 µm platinum/iridium wire). Hybrid stimulation, comprised of sub-threshold optical stimulation to ‘prime’ or raise the excitability of the neurons, lowered the threshold for electrical activation in most cases, but the impact on excitation width was more variable compared to transgenic mice. This study demonstrates the impact of opsin expression levels and expression pattern on optical and hybrid stimulation when considering optical or hybrid stimulation techniques for neuromodulation.

OBJECTIVE: Histological examination of cochleae from long-term cochlear implant users has shown evidence of particulate platinum (Pt) corroded from the surface of Pt electrodes. The pathophysiological effect of Pt within the cochlea has not been extensively investigated. We previously evaluated the effects of Pt corrosion in vivo using biphasic current pulses at high charge densities (≥ 267 μC/cm(2)/phase) and charge recovery using electrode shorting and found negligible pathophysiological impact. The present study extends this work by examining techniques that may reduce Pt corrosion. APPROACH: Deafened guinea pigs were continuously stimulated for 28 days using biphasic current pulses at extreme charge densities of up to 540 μC/cm(2)/phase using: (i) electrode shorting; (ii) electrode shorting with capacitive coupling (CC); or (iii) electrode shorting with alternating leading phase (AP). On completion of stimulation, cochleae were examined for corrosion product, tissue response, auditory nerve (AN) survival and trace levels of Pt; and electrodes examined for evidence of surface corrosion. MAIN RESULTS: Cochleae stimulated at ≥ 228 μC/cm(2)/phase showed particulate Pt, the extent of which was dependent on both charge density (p < 0.01) and charge recovery technique (p < 0.01); reduced Pt was evident in cochleae stimulated using CC or AP. Stimulation at charge densities ≥ 200 μC/cm(2)/phase resulted in significant electrode corrosion (p < 0.05); which was reduced using CC. Trace levels of Pt was reduced in cochleae stimulated with the addition of CC. Tissue response within cochleae increased with charge density (p < 0.007); cochleae stimulated at ≥ 200 μC/cm(2)/phase exhibited a vigorous response including a focal region of necrosis and macrophages. Notably, tissue response was not dependent on the charge recovery technique (p = 0.56). Finally, despite stimulation at high charge densities resulting in significant levels of Pt corrosion, there was no stimulus induced loss of ANs. SIGNIFICANCE: Significant increases in tissue response and Pt corrosion were observed following stimulation at high charge densities. Charge recovery using CC, and to a lesser extent AP, reduced the amount of Pt corrosion but not the tissue response. Despite chronic stimulation at change densities which are an order of magnitude higher than those used when programming cochlear implant recipients in the clinic, producing a vigorous tissue response and Pt corrosion products, there was no evidence of a stimulus induced loss of neurons.

Electrical stimulation has been used for decades in devices such as pacemakers, cochlear implants and more recently for deep brain and retinal stimulation and electroceutical treatment of disease. However, current spread from the electrodes limits the precision of neural activation, leading to a low quality therapeutic outcome or undesired side-effects. Alternative methods of neural stimulation such as optical stimulation offer the potential to deliver higher spatial resolution of neural activation. Direct optical stimulation is possible with infrared light, while visible light can be used to activate neurons if the neural tissue is genetically modified with a light sensitive ion channel. Experimentally, both methods have resulted in highly precise stimulation with little spread of activation at least in the cochlea, each with advantages and disadvantages. Infrared neural stimulation does not require modification of the neural tissue, but has very high power requirements. Optogenetics can achieve precision of activation with lower power, but only in conjunction with targeted insertion of a light sensitive ion channel into the nervous system via gene therapy. This review will examine the advantages and limitations of optical stimulation of neural tissue, using the cochlea as an exemplary model and recent developments for retinal and deep brain stimulation.

Electrical stimulation has long been the most effective strategy for evoking neural activity from bionic devices and has been used with great success in the cochlear implant to allow deaf people to hear speech and sound. Despite its success, the spread of electrical current stimulates a broad region of neural tissue meaning that contemporary devices have limited precision. Optical stimulation as an alternative has attracted much recent interest for its capacity to provide highly focused stimuli, and therefore, potentially improved sensory perception. Given its specificity of activation, optical stimulation may also provide a useful tool in the study of fundamental neuroanatomy and neurophysiological processes. Areas covered: This review examines the advances in optical stimulation - infrared, nanoparticle-enhanced, and optogenetic-based - and its application in the inner ear for the restoration of auditory function following hearing loss. Expert opinion: Initial outcomes suggest that optogenetic-based approaches hold the greatest potential and viability amongst optical techniques for application in the cochlea. The future success of this approach will be governed by advances in the targeted delivery of opsins to auditory neurons, improvements in channel kinetics, development of optical arrays, and innovation of opsins that activate within the optimal near-infrared therapeutic window.

Objective. Infrared light can be used to modulate the activity of neuronal cells through thermally-evoked capacitive currents and thermosensitive ion channel modulation. The infrared power threshold for action potentials has previously been found to be far lower in the in vivo cochlea when compared with other neuronal targets, implicating spiral ganglion neurons (SGNs) as a potential target for infrared auditory prostheses. However, conflicting experimental evidence suggests that this low threshold may arise from an intermediary mechanism other than direct SGN stimulation, potentially involving residual hair cell activity. Approach. Patch-clamp recordings from cultured SGNs were used to explicitly quantify the capacitive and ion channel currents in an environment devoid of hair cells. Neurons were irradiated by a 1870 nm laser with pulse durations of 0.2–5.0 ms and powers up to 1.5 W. A Hodgkin-Huxley-type model was established by first characterising the voltage dependent currents, and then incorporating laser-evoked currents separated into temperature-dependent and temperature-gradient-dependent components. This model was found to accurately simulate neuronal responses and allowed the results to be extrapolated to stimulation parameter spaces not accessible during this study. Main results. The previously-reported low in vivo SGN stimulation threshold was not observed, and only subthreshold depolarisation was achieved, even at high light exposures. Extrapolating these results with our Hodgkin-Huxley-type model predicts an action potential threshold which does not deviate significantly from other neuronal types. Significance. This suggests that the low-threshold response that is commonly reported in vivo may arise from an alternative mechanism, and calls into question the potential usefulness of the effect for auditory prostheses. The step-wise approach to modelling optically-evoked currents described here may prove useful for analysing a wider range of cell types where capacitive currents and conductance modulation are dominant.

Objective. Established guidelines for safe levels of electrical stimulation for neural prostheses are based on a limited range of the stimulus parameters used clinically. Recent studies have reported particulate platinum (Pt) associated with long-term clinical use of these devices, highlighting the need for more carefully defined safety limits. We previously reported no adverse effects of Pt corrosion products in the cochleae of guinea pigs following 4 weeks of electrical stimulation using charge densities far greater than the published safe limits for cochlear implants. The present study examines the histopathological effects of Pt within the cochlea following continuous stimulation at a charge density well above the defined safe limits for periods up to 6 months. Approach. Six cats were bilaterally implanted with Pt electrode arrays and unilaterally stimulated using charge balanced current pulses at a charge density of 267 μC cm−2 phase−1 using a tripolar electrode configuration. Electrochemical measurements were made throughout the implant duration and evoked potentials recorded at the outset and on completion of the stimulation program. Cochleae were examined histologically for particulate Pt, tissue response, and auditory nerve survival; electrodes were examined for surface corrosion; and cochlea, brain, kidney, and liver tissue analysed for trace levels of Pt. Main results. Chronic stimulation resulted in both a significant increase in tissue response and particulate Pt within the tissue capsule surrounding the electrode array compared with implanted, unstimulated control cochleae. Importantly, there was no stimulus-induced loss of auditory neurons (ANs) or increase in evoked potential thresholds. Stimulated electrodes were significantly more corroded compared with unstimulated electrodes. Trace analysis revealed Pt in both stimulated and control cochleae although significantly greater levels were detected within stimulated cochleae. There was no evidence of Pt in brain or liver; however, trace levels of Pt were recorded in the kidneys of two animals. Finally, increased charge storage capacity and charge injection limit reflected the more extensive electrode corrosion associated with stimulated electrodes. Significance. Long-term electrical stimulation of Pt electrodes at a charge density well above existing safety limits and nearly an order of magnitude higher than levels used clinically, does not adversely affect the AN population or reduce neural function, despite a stimulus-induced tissue response and the accumulation of Pt corrosion product. The mechanism resulting in Pt within the unstimulated cochlea is unclear, while the level of Pt observed systemically following stimulation at these very high charge densities does not appear to be of clinical significance.

Infrared light can be used to modulate the activity of neuronal cells with broad generality and without any need for exogenous materials. The action potential response has been shown to be associated with heating due to the absorption of light by water in and around the illuminated tissues, which gives rise to at least two distinct processes: namely, the temperature pulses cause depolarizing capacitive currents due to an intramembrane thermo-mechanical effect, and in addition, temperature-sensitive TRPV ion channels (and likely, voltage-gated channels) drive additional membrane depolarization. However, substantial differences between the activation threshold of primary auditory neurons ( 300 mJ/cm^2) in vivo have generated some controversy in the field. A temperature-dependent Hodgkin-Huxley type model, which combines capacitive currents and the experimentally-derived characteristics of voltage-gated potassium and sodium ion channels in primary auditory neurons, was used to accurately explain the in vitro response to 1870 nm infrared illumination. TRPV channels do not make a significant contribution in this case, suggesting that the detailed mechanism of the neuronal response to infrared light is dependent on the specific cell type. Furthermore, based on this detailed understanding of the cell behaviour, it is shown that action potentials cannot be generated at safe laser power levels. This suggests that the previously reported response of the auditory system to infrared stimulation in vivo might arise from a different mechanism, and calls into question the potential usefulness of the effect for auditory prostheses.

Objective The performance of neuroprostheses, including cochlear and retinal implants, is currently constrained by the spatial resolution of electrical stimulation. Optogenetics has improved the spatial control of neurons in vivo but lacks the fast-temporal dynamics required for auditory and retinal signalling. The objective of this study is to demonstrate that combining optical and electrical stimulation in vitro could address some of the limitations associated with each of the stimulus modes when used independently. Approach The response of murine auditory neurons expressing ChR2-H134 to combined optical and electrical stimulation was characterised using whole cell patch clamp electrophysiology. Main results Optogenetic costimulation produces a three-fold increase in peak firing rate compared to optical stimulation alone and allows spikes to be evoked by combined subthreshold optical and electrical inputs. Subthreshold optical depolarisation also facilitated spiking in auditory neurons for periods of up to 30 ms without evidence of wide-scale Na+ inactivation. Significance These findings may contribute to the development of spatially and temporally selective optogenetic-based neuroprosthetics and complement recent developments in 'fast opsins'.

A model to simulate heating as a result of pulse repetitions during infrared neural stimulation (INS), with both single- and multiple-emitters is presented. This model allows the temperature increases from pulse trains rather than single pulses to be considered. The model predicts that using a stimulation rate of 250 Hz with typical laser parameters at a single stimulation site results in a temperature increase of 2.3°C. When multiple stimulation sites are used in analogy to cochlear implants, the temperature increases further depending upon the spacing between emitters. However, when the light is more localized at multiple stimulation sites the temperature increase is reduced.

The effect of macrobending on fiber Bragg gratings (FBGs) in standard and specialist use single-mode fibers has been investigated for bend diameters down to 6 mm. The bend dependence of various spectral properties of FBGs, including center wavelength, were found to depend upon fiber type. A maximum centre wavelength shift of 0.39 nm was measured for a FBG written in low bend loss fiber bent to a 6 mm diameter. To investigate the cause of the observed wavelength shift, and the dependence on fiber design, a number of theoretical models have been applied to the problem. The results of modeling suggest that bend-induced changes in mode structure may explain the observed differences between fiber types, while wavefront distortion might be the cause of the general shift to shorter FBG center wavelengths when the bend diameter decreases.

The sugarIbase correlation of cytosine (base) and deoxyribose (sugar) moieties of cytidine is investigated based on their inner-shell electronic structura li nformation. A recently developed density functional theory (DFT) model ,C VB3LYP, with a Gaussian-type basis set of 6-311G**, and the DFT-LB94 model with a Slater-type basis set of TZ2P are employed to calculate inner shell ionization energies. The results reveal that the corresponding geometry of cytidine is not significantl yd ifferent from its fragments, i.e., cytosine and deoxyribose. Changes in charge distribution of cytidine with respect to cytosine and deoxyribose concentrate on the local Cs ites in the base pyrimidine ring and sugar ring, as indicated by the atomi cH irshfeld charges. The O-K, N-K, and C-K spectra of cytidine inherit the aromati cs ignature in cytosine, suggesting that the rol eo f the aromati cr ing i sab uffer to diffuse the changes brought in by the addition of the deoxyribose moiety. Formation of cytidine, however, substantially changes the C-K spectra of the deoxyribose moiety. In general, the correlated O-K, N-K, and C-K sites of cytidine exhibit small red shifts with respect to the cytosine base, whereas the O-K and C-K sites of cytidine show blue shifts in comparison with those of deoxyribose.

Objective Recent research has demonstrated that nerves can be stimulated by transient heating associated with the absorption of infrared light by water in the tissue. There is a great deal of interest in using this technique in neural prostheses, due to the potential for increased localization of the stimulus and minimization of contact with the tissue. However, thermal modelling suggests that the full benefits of increased localization may be reduced by cumulative heating effects when multiple stimulus sites and/or high repetition rates are used. Approach Here we review recent in vitro and in vivo results suggesting that the transient heating associated with plasmon absorption in gold nanorods can also be used to stimulate nerves. Main results Patch clamp experiments on cultured spiral ganglion neurons exhibited action potentials when exposed to 780 nm light at the plasmon absorption peak, while the amplitude of compound action potentials in the rat sciatic nerve were increased by laser irradiation of gold nanorods in the vicinity of the plasma membrane. Similarly, calcium imaging studies of NG108-15 neuronal cells incubated with Au nanorods revealed an increased level of intracellular calcium activity synchronized with laser exposure. Significance Given that the plasmon absorption peak of gold nanorods can be matched with the transparency window of biological tissues, these results demonstrate that nanorod absorbers hold great promise to enhance the process of infrared neural stimulation for future applications in neural prostheses and fundamental studies in neuroscience.

At present there is some debate as to the processes by which infrared neural stimulation (INS) activates neurons in the cochlea, as the lasers used for INS can potentially generate a range of secondary stimuli e.g. an acoustic stimulus is produced when the light is absorbed by water. To clarify whether INS in the cochlea requires functioning hair cells and to explore the potential relevance to cochlear implants, experiments using INS were performed in the cochleae of both normal hearing and profoundly deaf guinea pigs. A response to laser stimulation was readily evoked in normal hearing cochlea. However, no response was evoked in any profoundly deaf cochleae, for either acute or chronic deafening, contrary to previous work where a response was observed after acute deafening with ototoxic drugs. A neural response to electrical stimulation was readily evoked in all cochleae after deafening. The absence of a response from optical stimuli in profoundly deaf cochleae suggests that the response from INS in the cochlea is hair cell mediated.

Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential.

A model of infrared neural stimulation (INS) has been developed to allow the temporal characteristics of different stimulation parameters and geometries to be better understood. The model uses a finite element approach to solve the heat equation and allow detailed analysis of heat during INS with both microsecond and millisecond laser pulses. When compared with experimental data, the model provides insight into the mechanisms behind INS. In particular, the analysis suggests that there may be two broad regimes of INS: the process tends to be limited by the total pulse energy for pulse lengths below 100 μs, while the temperature gradient with respect to time becomes more important above 100 μs.

Infrared neural stimulation (INS) is a novel technique for stimulating neurons with infrared light, rather than the traditional electrical means. There has been significant discussion in the literature on the mechanisms behind INS, while recent work has shown that infrared light stimulates neurons by causing a reversible change in their membrane capacitance. Nevertheless, the effect of different laser parameters on neuronal responses is still not well understood. To better understand this and to assist in designing light delivery systems, modelling of spatial and temporal characteristics of light delivery during INS has been performed. Monte Carlo modelling of photon transport in tissue allows the spatial characteristics of light to be determined during INS and allows comparisons of varying geometries and fibre designs. Finite element analysis of heat conduction can then be used to reveal the behavior of different pulse durations and the resulting temperature decay. The combination of the two methods allows for further insights into the mechanisms of INS and assists in understanding different mechanisms which promote INS. The model suggests there may be two regimes of INS, namely temperature limited for pulses under 100 μs and temperature gradient limited for longer pulses. this is compatible with previously published data, but requires further experimentation for confirmation. The model also provides a tool for optimising the design of emitters and implants.

Sensing and telecommunication applications requiring the bending of optical fibers to small diameters are on the increase. Recent work has shown that the centre wavelength of fiber Bragg gratings has a bend dependence the magnitude of which varies with the type of fiber in which the grating is written. In this work the basis of the centre wavelength shift is investigated by modeling the effects of several potential causes for standard and depressed cladding fiber designs. The majority of the expected affects, including bend induced stress and mode field deformation, were found to result in small wavelength shifts in the opposite direction to those observed experimentally. However, a new account of the shift, based on simplistic geometrical optics, does show wavelength changes in the observed direction, of up to -0.15 nm, which is in the range of the experimentally measured shifts.

Optical fibers are finding increased usage in biomedical applications, during which the fibers are often subjected to bending. Bending optical fibers can affect transmission properties and increase the likelihood of failure. In this paper the bending of fibers is discussed in relation to biomedical and sensing applications.

The effects of relatively small bend diameters on fibre Bragg gratings written in standard and low bend loss fibre have been investigated. Results including Bragg wavelength shifts with bending are reported.

Gravitational lensing calculation using a direct inverse ray-shooting approach is a computationally expensive way to determine magnification maps, caustic patterns, and light-curves (e.g. as a function of source profile and size). However, as an easily parallelisable calculation, gravitational ray-shooting can be accelerated using programmable graphics processing units (GPUs). We present our implementation of inverse ray-shooting for the NVIDIA G80 generation of graphics processors using the NVIDIA Compute Unified Device Architecture (CUDA) software development kit. We also extend our code to multiple-GPU systems, including a 4-GPU NVIDIA S1070 Tesla unit. We achieve sustained processing performance of 182 Gflop/s on a single GPU, and 1.28 Tflop/s using the Tesla unit. We demonstrate that billion-lens microlensing simulations can be run on a single computer with a Tesla unit in timescales of order a day without the use of a hierarchical tree code., Comment: 21 pages, 4 figures, submitted to New Astronomy

Chicken parathyroid hormone (cPTH) has been reported to stimulate adrenal steroidogenesis and to have unusual potency on traditional PTH target tissues. To evaluate these properties, chicken PTH-(1-88) has been expressed in Escherichia coli using a plasmid encoding a fusion protein which links together growth hormone, a factor Xa recognition site, and chicken PTH-(1-88). The growth hormone-cPTH fusion protein required the presence of 0.02% sodium dodecyl sulfate to remain in solution and be cleaved by factor Xa. The high performance liquid chromatography-purified recombinant cPTH-(1-88) and chemically synthesized cPTH-(1-34) had similar potency in rat osteosarcoma (ROS 17/2.8) cells, opossum kidney (OK) cells, and dispersed primary chicken kidney cells. The biologic potencies of cPTH-(1-34) and cPTH-(1-88) in radioreceptor binding and cAMP generation in both bone- and kidney-derived cell lines were less than those of human (h)PTH-(1-34). In dispersed chicken kidney cells, cAMP production by cPTH-(1-34) and cPTH-(1-88) was similar to that stimulated by human PTH-(1-34). No stimulation of steroidogenesis could be detected when recombinant chicken PTH-(1-88) was added to dispersed chicken adrenal cells. The biologic activity of recombinant chicken PTH-(1-88) purified from E. coli was comparable with that of chicken PTH-(1-88) expressed by mammalian COS cells. Thus, the full-length chicken PTH did not exhibit enhanced potency, when compared with human PTH in ROS 17/2.8, OK cell lines, and dispersed chicken kidney cells and did not demonstrate the novel steroidogenic action previously reported in adrenal cells. The successful production of chicken PTH-(1-88) will enhance our understanding of the structure-activity relationships for PTH, particularly the sequence-dependent metabolism of the hormone.

A Monte Carlo model has been developed to simulate light transport and absorption in neural tissue during infrared neural stimulation (INS). A range of fiber core sizes and numerical apertures are compared illus- trating the advantages of using simulations when designing a light delivery system. A range of wavelengths, com- monly used for INS, are also compared for stimulation of nerves in the cochlea, in terms of both the energy absorbed and the change in temperature due to a laser pulse. Modeling suggests that a fiber with core diameter of 200 μm and NA ¼ 0.22 is optimal for optical stimulation in the geometry used and that temperature rises in the spiral ganglion neurons are as low as 0.1°C. The results show a need for more careful experimentation to allow different proposed mechanisms of INS to be distinguished. © 2012 Society of Photo-Optical Instrumentation Engineers

The effects of bending on the spectral characteristics of fibre Bragg gratings have been investigated at relatively small bend diameters for small form factor applications. Tests undertaken on Bragg gratings written in different types of singlemode optical fibre indicate that the fibre type influences the magnitude of observed changes. Shifts in the centre wavelength of ∼0.35 nm have been measured for a low bend loss fibre when the bend diameter was reduced to 6 mm. In contrast, no consistent trend could be observed for Bragg gratings in standard SMF-28 optical fibre as a function of bend diameter, despite the higher losses exhibited in this case.

A simple, self-diagnostic strain sensor is described, based on a strongly reflective optical fibre Bragg grating illuminated by a broadband source. The total reflected power from these gratings is shown to be a function of the strain gradient experienced by the grating. This is because a change in pitch within a section of the grating results in the emergence of reflected energy in other spectral regions, without any significant reduction in the peak intensity at the Bragg wavelength. Thus, the presence of a localized strain can be inferred directly from an intensity measurement without the need for an optical filter or other more complex interrogation schemes. For spectrally flat light sources, the measurement is relatively insensitive to environmental temperature changes. The sensing mechanism can also be considered 'self-diagnostic' as a signal is returned by the grating even under zero load unless the sensor has failed. Modelling results are presented to determine the minimum grating strength required to achieve this effect, while the technique has been experimentally verified by measuring the strain transfer on a loaded scarf repair joint at room and elevated temperatures. The scarf repair was loaded to failure and a reduction in strain transfer was observed as the failure grew along the bondline, in accordance with finite element modelling results.