Genotoxicity of inorganic lead salts and disturbance of microtubule function

Lead compounds are known genotoxicants, principally affecting the integrity of chromosomes. Lead chloride and lead acetate induced concentration-dependent increases in micronucleus frequency in V79 cells, starting at 1.1 μ M lead chloride and 0.05 μ M lead acetate. The difference between the lead salts, which was expected based on their relative abilities to form complex acetato-cations, was confirmed in an independent experiment. CREST analyses of the micronuclei verified that lead chloride and acetate were predominantly aneugenic (CREST-positive response), which was consistent with the morphology of the micronuclei (larger micronuclei, compared with micronuclei induced by a clastogenic mechanism). The effects of high concentrations of lead salts on the microtubule network of V79 cells were also examined using immunofluorescence staining. The dose effects of these responses were consistent with the cytotoxicity of lead(II), as visualized in the neutral-red uptake assay. In a cell-free system, 20-60 μ M lead salts inhibited tubulin assembly dose-dependently. The no-observed-effect concentration of lead(II) in this assay was 10 μ M. This inhibitory effect was interpreted as a shift of the assembly/disassembly steady-state toward disassembly, e.g., by reducing the concentration of assembly-competent tubulin dimers. The effects of lead salts on microtubule-associated motor-protein functions were studied using a kinesin-gliding assay that mimics intracellular transport processes in vitro by quantifying the movement of paclitaxel-stabilized microtubules across a kinesin-coated glass surface. There was a dose-dependent effect of lead nitrate on microtubule motility. Lead nitrate affected the gliding velocities of microtubules starting at concentrations above 10 μ M and reached half-maximal inhibition of motility at about 50 μ M. The processes reported here point to relevant interactions of lead with tubulin and kinesin at low dose levels. Environ. Mal. Mutagen. 45:346-353, 2005. © 2005 Wiley-Liss, Inc.

Population-based continuous optimization, probabilistic modelling and mean shift

Evolutionary algorithms perform optimization using a population of sample solution points. An interesting development has been to view population-based optimization as the process of evolving an explicit, probabilistic model of the search space. This paper investigates a formal basis for continuous, population-based optimization in terms of a stochastic gradient descent on the Kullback-Leibler divergence between the model probability density and the objective function, represented as an unknown density of assumed form. This leads to an update rule that is related and compared with previous theoretical work, a continuous version of the population-based incremental learning algorithm, and the generalized mean shift clustering framework. Experimental results are presented that demonstrate the dynamics of the new algorithm on a set of simple test problems.

Interhemispheric differences of spectral power in expressive language:a MEG study with clinical applications

In the last decade we have seen an exponential growth of functional imaging studies investigating multiple aspects of language processing. These studies have sparked an interest in applying some of the paradigms to various clinically relevant questions, such as the identification of the cortical regions mediating language function in surgical candidates for refractory epilepsy. Here we present data from a group of adult control participants in order to investigate the potential of using frequency specific spectral power changes in MEG activation patterns to establish lateralisation of language function using expressive language tasks. In addition, we report on a paediatric patient whose language function was assessed before and after a left hemisphere amygdalo-hippocampectomy. Our verb generation task produced left hemisphere decreases in beta-band power accompanied by right hemisphere increases in low beta-band power in the majority of the control group, a previously unreported phenomenon. This pattern of spectral power was also found in the patient's post-surgery data, though not her pre-surgery data. Comparison of pre and post-operative results also provided some evidence of reorganisation in language related cortex both inter- and intra-hemispherically following surgery. The differences were not limited to changes in localisation of language specific cortex but also changes in the spectral and temporal profile of frontal brain regions during verb generation. While further investigation is required to establish concordance with invasive measures, our data suggest that the methods described may serve as a reliable lateralisation marker for clinical assessment. Furthermore, our findings highlight the potential utility of MEG for the investigation of cortical language functioning in both healthy development and pathology.

Grouping and the pitch of a mistuned fundamental component:effects of applying simultaneous multiple mistunings to the other harmonics

Mistuning a harmonic produces an exaggerated change in its pitch. This occurs because the component becomes inconsistent with the regular pattern that causes the other harmonics (constituting the spectral frame) to integrate perceptually. These pitch shifts were measured when the fundamental (F0) component of a complex tone (nominal F0 frequency = 200 Hz) was mistuned by +8% and -8%. The pitch-shift gradient was defined as the difference between these values and its magnitude was used as a measure of frame integration. An independent and random perturbation (spectral jitter) was applied simultaneously to most or all of the frame components. The gradient magnitude declined gradually as the degree of jitter increased from 0% to ±40% of F0. The component adjacent to the mistuned target made the largest contribution to the gradient, but more distant components also contributed. The stimuli were passed through an auditory model, and the exponential height of the F0-period peak in the averaged summary autocorrelation function correlated well with the gradient magnitude. The fit improved when the weighting on more distant channels was attenuated by a factor of three per octave. The results are consistent with a grouping mechanism that computes a weighted average of periodicity strength across several components. © 2006 Elsevier B.V. All rights reserved.

Simulation of optical fibre communication systems influenced by stimulated brillouin scattering

Boyd's SBS model which includes distributed thermal acoustic noise (DTAN) has been enhanced to enable the Stokes-spontaneous density depletion noise (SSDDN) component of the transmitted optical field to be simulated, probably for the first time, as well as the full transmitted field. SSDDN would not be generated from previous SBS models in which a Stokes seed replaces DTAN. SSDDN becomes the dominant form of transmitted SBS noise as model fibre length (MFL) is increased but its optical power spectrum remains independent of MFL. Simulations of the full transmitted field and SSDDN for different MFLs allow prediction of the optical power spectrum, or system performance parameters which depend on this, for typical communication link lengths which are too long for direct simulation. The SBS model has also been innovatively improved by allowing the Brillouin Shift Frequency (BS) to vary over the model fibre length, for the nonuniform fibre model (NFM) mode, or to remain constant, for the uniform fibre model (UFM) mode. The assumption of a Gaussian probability density function (pdf) for the BSF in the NFM has been confirmed by means of an analysis of reported Brillouin amplified power spectral measurements for the simple case of a nominally step-index single-mode pure silica core fibre. The BSF pdf could be modified to match the Brillouin gain spectra of other fibre types if required. For both models, simulated backscattered and output powers as functions of input power agree well with those from a reported experiment for fitting Brillouin gain coefficients close to theoretical. The NFM and UFM Brillouin gain spectra are then very similar from half to full maximum but diverge at lower values. Consequently, NFM and UFM transmitted SBS noise powers inferred for long MFLs differ by 1-2 dB over the input power range of 0.15 dBm. This difference could be significant for AM-VSB CATV links at some channel frequencies. The modelled characteristic of Carrier-to-Noise Ratio (CNR) as a function of input power for a single intensity modulated subcarrier is in good agreement with the characteristic reported for an experiment when either the UFM or NFM is used. The difference between the two modelled characteristics would have been more noticeable for a higher fibre length or a lower subcarrier frequency.

Retinal and systemic vascular function in health and disease: the effect of smoking and coronary artery disease

The purpose of the following studies was to explore the effect of systemic vascular and endothelial dysfunction upon the ocular circulation and functionality of the retina. There are 6 principal sections to the present work. Retinal vessel activity in smokers and non-smokers: the principal findings of this work were: chronic smoking affects retinal vessel motion at baseline and during stimulation with flickering light; chronic smoking leads to a vaso-constrictory shift in retinal arteriolar reactivity to flicker; retinal arteriolar elasticity is decreased in chronic smokers. The effect of acute smoking on retinal vessel dynamics in smokers and non-smokers: the principal finding of this work was that retinal reactivity in chronic smokers is blunted when exposed to clicker light provocation immediately after smoking one cigarette. Ocular blood flow in coronary artery disease: The principal findings of this work were: retrobulbar and retinal blood flow is preserved in CAD patients, despite a change pulse wave transmission; arterial retinal response to flickering light provocation is significantly delayed in CAD patients; retinal venular diameters are significantly dilated in CAD patients. Autonomic nervous system function and peripheral circulation in CAD: The principal findings in this work were: CAD patients demonstrate a sympathetic overdrive during a 24 period; a delay in peripheral vascular reactivity (nail-fold capillaries) as observed in patients suffering from CAD could be caused by either arteriosclerotic changes of the vascular walls or due to systemic haemodynamic changes. Visual function in CAD: The principal findings in this work were: overall visual function in CAD patients is preserved, despite a decrease in contrast sensitivity; applying a filtering technique selecting those with greater coefficient of variance which in turn represents a decrease in reliability, some patients appear to have an impaired visual function as assessed using FDT visual field evaluation. Multiple functional, structural and biochemical vascular endothelial dysfunctions in patients suffering from CAD: relationships and possible implications: The principal findings of this work were: BMI significantly correlated with vWF (a marker of endothelial function) in CAD patients. Retinal vascular reactivity showed a significant correlation with peripheral reactivity parameters in controls which lacked in the CAD group and could reflect a loss in vascular endothelial integrity; visual field parameters as assessed by frequency doubling technology were strongly related with systemic vascular elasticity (ambulatory arterial stiffness index) in controls but not CAD patients.

Phase shift keyed systems based on a gain switched laser transmitter

Return-to-Zero (RZ) and Non-Return-to-Zero (NRZ) Differential Phase Shift Keyed (DPSK) systems require cheap and optimal transmitters for widespread implementation. The authors report on a gain switched Discrete Mode (DM) laser that can be employed as a cost efficient transmitter in a 10.7 Gb/s RZ DPSK system and compare its performance to that of a gain switched Distributed Feed-Back (DFB) laser. Experimental results show that the gain switched DM laser readily provides error free performance and a receiver sensitivity of -33.1 dBm in the 10.7 Gbit/s RZ DPSK system. The standard DFB laser on the other hand displays an error floor at 10(-1) in the same RZ DPSK system. The difference in performance, between the two types of gain switched transmitters, is analysed by investigating their linewidths. We also demonstrate, for the first time, the generation of a highly coherent gain switched pulse train which displays a spectral comb of approximately 13 sidebands spaced by the 10.7 GHz modulation frequency. The filtered side-bands are then employed as narrow linewidth Continuous Wave (CW) sources in a 10.7 Gb/s NRZ DPSK system.

Design of Raman-based nonlinear loop mirror for all-optical 2R regeneration of differential phase-shift-keying transmission

We present a concept for all-optical regeneration of signals modulated in phase-sensitive modulation formats, which is based on a new design of Raman amplified nonlinear optical loop mirror (RA-NOLM). We demonstrate simultaneous amplitude-shape regeneration and phase-noise reduction in high-speed differential phase-shift-keying transmission systems by use of the RA-NOLM combined with spectral filtering.

Bend induced spectral changes in fibre Bragg gratings and their applications for simultaneous measurement

A report is presented on the interesting bending effect of cladding mode resonances in fibre Bragg gratings (FBGs). It is observed that a serial of new cladding mode resonances can arise under bending and the new and the original cladding mode resonances have opposite trends in amplitude change and wavelength shift when the curvature varies. The discovery provides an effective new way to discriminate between bend and strain or bend and temperature when using only a single uniform FBG.

Enhanced spectral sensitivity of fibre long period gratings to refractive index of aqueous solutions utilising copper patterned coatings

A set of long period grating devices have been fabricated in photosensitive single mode fibre coated with a series of copper rings (period of 380μm, 50% duty cycle and length of 4cm). The long period gratings were inscribed with a uniform UV-laser exposure across the entire length of the copper ring patterned coating. The devices ranged in copper thickness from 0.5μm to 1.5μm. In addition, a control long period grating was fabricated in the same type of fibre with the same period for comparison. The refractive index and temperature spectral sensitivity of these devices were investigated and it was found that the index and temperature sensitivity is a function of the thickness of the copper rings, as supported by theoretical modelling. Furthermore, the index sensitivity of these devices in the 1.333 index region is greater than the control long period grating. The patterned 0.5μm coated long period grating gave a sensitivity of Δλ/Δn = -74 nm leading to a resolution of 1.4×10-3 compared to the control which had a sensitivity of Δλ/Δn = -32 nm with a resolution of 3.2×10-3 in the index region of 1.320 to 1.380 (aqueous solution regime). This demonstrates a two fold increase in the sensitivity. This novel fibre long period grating device shows potential for increasing the resolution of measurements of the index of aqueous solutions.

A comparison of the spectral properties of high temperature annealed long period gratings inscribed by fs laser, UV and fusion-arc

Long period gratings have been inscribed in standard single mode fibre using a fs laser system, a fusion arc and a UV laser and a comparative study carried out of their thermal behaviour. The fs laser induced gratings can survive temperatures in excess of 800°C, however the inscription process can induce considerable birefringence within the device. Annealing studies have been carried out showing that below 600°C, all three grating types show a blue shift in their room temperature resonance wavelengths following cyclic heating, while above 600°C, the UV and arc induced LPGs exhibit a red shift, with the fs LPG showing an even stronger blue shift. High temperature annealing is also shown to considerably reduce the birefringence induced by the fs inscription process.

True chemical shift correlation maps:a TOCSY experiment with pure shifts in both dimensions

Signal resolution in H NMR is limited primarily by multiplet structure. Recent advances in pure shift NMR, in which the effects of homonuclear couplings are suppressed, have allowed this limitation to be circumvented in 1D NMR, gaining almost an order of magnitude in spectral resolution. Here for the first time an experiment is demonstrated that suppresses multiplet structure in both domains of a homonuclear two-dimensional spectrum. The principle is demonstrated for the TOCSY experiment, generating a chemical shift correlation map in which a single peak is seen for each coupled relationship, but the principle is general and readily extensible to other homonuclear correlation experiments. Such spectra greatly simplify manual spectral analysis and should be well-suited to automated methods for structure elucidation. © 2010 American Chemical Society.

Bend induced spectral changes in fibre Bragg gratings and their applications for simultaneous measurement

A report is presented on the interesting bending effect of cladding mode resonances in fibre Bragg gratings (FBGs). It is observed that a serial of new cladding mode resonances can arise under bending and the new and the original cladding mode resonances have opposite trends in amplitude change and wavelength shift when the curvature varies. The discovery provides an effective new way to discriminate between bend and strain or bend and temperature when using only a single uniform FBG.

Design of Raman-based nonlinear loop mirror for all-optical 2R regeneration of differential phase-shift-keying transmission

We present a concept for all-optical regeneration of signals modulated in phase-sensitive modulation formats, which is based on a new design of Raman amplified nonlinear optical loop mirror (RA-NOLM). We demonstrate simultaneous amplitude-shape regeneration and phase-noise reduction in high-speed differential phase-shift-keying transmission systems by use of the RA-NOLM combined with spectral filtering. © 2006 IEEE.

Pulse shaping in mode-locked fiber lasers by in-cavity spectral filter

We numerically show the possibility of pulse shaping in a passively mode-locked fiber laser by inclusion of a spectral filter into the laser cavity. Depending on the amplitude transfer function of the filter, we are able to achieve various regimes of advanced temporal waveform generation, including ones featuring bright and dark parabolic-, flat-top-, triangular- and saw-tooth-profiled pulses. The results demonstrate the strong potential of an in-cavity spectral pulse shaper for controlling the dynamics of mode-locked fiber lasers. © 2014 Optical Society of America.