Mechanisms of anticholinesterase-induced myopathy and its prevention

In the introduction a brief outline of the possible mechanisms involved in the process of cellular necrosis with particular emphasis on skeletal muscle necrosis after antiChE is discussed. Ecothiopate (ECO), an antiChE, was shown to produce dose-dependent inhibition of both AChE and BuChE in diaphragm and blood of mice. Inhibition of AChE resulted in dose-dependent influx of calcium at the junctional region with the consequent development of morphological and biochemical alterations. Non-necrotising doses of ECO caused hypercontractions of varying severity, distorted end plate and slight elevation of serum creatine kinase (CK). Necrotising doses of ECO further caused contraction clumps, loss of striations and procion staining with high serum CK. The extent of ECO-induced myopathy depended on entry of extracellular calcium rather than the degree of AChE inhibition. The essential Ca2+ mediated process(es) in ECO-induced myopathy was thought to be the generation of superoxide and superoxide-derived free radicals and/or lipid peroxidation. Mitochondria and xanthine oxidase may be the major contributors to the generation of superoxide. No evidence was found for the depletion of high energy phosphates. ECO-induced myopathy could be successfully prevented by prior administration of pyridostigmine or various antioxidants, the most effective being Vit E or Vit E + N-acetylcysteine. Allopurinol or N-acetylcysteine alone were also effective. However, the use of a wide range of membrane end plate channel blockers or non-quantal release blockers were unsuccessful in the prevention of ECO-induced myopathy.

The development of an in vivo model of drug-induced terminal differentiation of Leukaemic cells

The technique of growing human leukaemic cells in diffusion chambers was developed to enable chemicals to be assessed for their ability to induce terminal differentiation. HL-60 promyelocytic leukaemia cell growth, in a lucite chamber with a Millipore filter, was optimised by use of a lateral incision site. Chambers were constructed using 0.45um filters and contained 150ul of serum-free HL-60 cells at a density of 1x106 cells/ml. The chambers were implanted into CBA/Ca mice and spontaneous terminal differentiation of the cells to granulocytes was prevented by the use of serum-free medium. Under these conditions there was an initial growth lag of 72 hours and a logarithmic phase of growth for 96 hours; the cell number reached a plateau after 168 hours of culture in vivo. The amount of drug in the plasma of the animal and in chambers that had been implanted for 5 days, was determined after a single ip injection of equitoxic doses of N-methylformamide, N-ethylformamide, tetramethylurea, N-dibutylformamide, N-tetramethylbutylformamide and hexamethylenebisacetamide. Concentrations of both TMU and HMBA were obtained in the plasma and in the chamber which were pharmacologically effective for the induction of differentiation of HL-60 cells in vitro, that is 12mM TMU and 5mM HMBA. A 4 day regime of treatment of animals implanted with chambers demonstrated that TMU and HMBA induced terminal differentiation of 50% and 35%, respectively, of the implanted HL-60 cells to granulocyte-like cells, assessed by measurement of functional and biochemical markers of maturity. None of the other agents attained concentrations in the plasma that were pharmacologically effective for the induction of differentiation of the cells in vitro and were unable to induce the terminal differentiation of the cells in vivo.

Generation of triangular pulses in normally dispersive fibre

In this scheme, nonlinearity and dispersion in the NDF lead to various reshaping processes of an initial, conventional pulse according to the chirping value and power level at the input of the fibre. In particular, we have observed that triangular-shaped pulses can be generated for sufficiently high energies and a positive initial chirp parameter. In our experiments, 2.8 ps-FWHM, transform-limited pulses generated from a mode-locked fibre laser source at a repetition rate of 1.25 GHz were pre-chirped by propagating the pulses through different lengths of standard mono-mode fibre. The chirped pulses were then amplified to different power levels before being launched into a 2.3 km section of True Wave fibre (TWF). The corresponding numerically calculated pulse temporal intensity profile and numerical and experimental second-harmonic generation frequency-resolved optical gating (SHG FROG) spectrograms were also derived. In conclusion, we have presented numerical modelling results which show the system design parameters required for the generation of triangular-shaped pulses in a nonlinear NDF, and experimentally demonstrated triangular pulse shaping in conventional NDF.

Femtosecond laser-induced microstructures on diamond for microfluidic sensing devices applications

This paper reported a three-dimensional microfluidic channel structure, which was fabricated by Yb:YAG 1026?nm femtosecond laser irradiation on a single-crystalline diamond substrate. The femtosecond laser irradiation energy level was optimized at 100?kHz repetition rate with a sub-500 femtosecond pulse duration. The morphology and topography of the microfluidic channel were characterized by a scanning electron microscope and an atomic force microscope. Raman spectroscopy indicated that the irradiated area was covered by graphitic materials. By comparing the cross-sectional profiles before/after removing the graphitic materials, it could be deduced that the microfluidic channel has an average depth of ~410?nm with periodical ripples perpendicular to the irradiation direction. This work proves the feasibility of using ultra-fast laser inscription technology to fabricate microfluidic channels on biocompatible diamond substrates, which offers a great potential for biomedical sensing applications.

Femtosecond laser-induced microstructures on diamond for microfluidic sensing device applications

This paper reported a three-dimensional microfluidic channel structure, which was fabricated by Yb:YAG 1026?nm femtosecond laser irradiation on a single-crystalline diamond substrate. The femtosecond laser irradiation energy level was optimized at 100?kHz repetition rate with a sub-500 femtosecond pulse duration. The morphology and topography of the microfluidic channel were characterized by a scanning electron microscope and an atomic force microscope. Raman spectroscopy indicated that the irradiated area was covered by graphitic materials. By comparing the cross-sectional profiles before/after removing the graphitic materials, it could be deduced that the microfluidic channel has an average depth of ~410?nm with periodical ripples perpendicular to the irradiation direction. This work proves the feasibility of using ultra-fast laser inscription technology to fabricate microfluidic channels on biocompatible diamond substrates, which offers a great potential for biomedical sensing applications.

Intracavity generation of 610nm light by periodically poled near-stoichiometric lithium tantalate

Intracavity frequency doubling of an optically pumped GaInNAs semiconductor disk laser by a periodically poled near-stoichiometric lithium tantalate crystal has been investigated. Stable second-harmonic generation at 610nm has been achieved with an output power of 730mW, limited only by the spectral acceptance range and Fresnel losses of the crystal. Spectral tuning of 8nm was realised with a Fabry-Pérot etalon. © The Institution of Engineering and Technology.

Femtosecond laser-induced microstructures on diamond for microfluidic sensing devices applications

This paper reported a three-dimensional microfluidic channel structure, which was fabricated by Yb:YAG 1026?nm femtosecond laser irradiation on a single-crystalline diamond substrate. The femtosecond laser irradiation energy level was optimized at 100?kHz repetition rate with a sub-500 femtosecond pulse duration. The morphology and topography of the microfluidic channel were characterized by a scanning electron microscope and an atomic force microscope. Raman spectroscopy indicated that the irradiated area was covered by graphitic materials. By comparing the cross-sectional profiles before/after removing the graphitic materials, it could be deduced that the microfluidic channel has an average depth of ~410?nm with periodical ripples perpendicular to the irradiation direction. This work proves the feasibility of using ultra-fast laser inscription technology to fabricate microfluidic channels on biocompatible diamond substrates, which offers a great potential for biomedical sensing applications.

The role of Ca2+ in the generation of spontaneous astrocytic Ca2+ oscillations

Astrocytes in the rat thalamus display spontaneous [Ca2+]i oscillations that are due to intracellular release, but are not dependent on neuronal activity. In this study we have investigated the mechanisms involved in these spontaneous [Ca2+]i oscillations using slices loaded with Fluo-4 AM (5 μM) and confocal microscopy. Bafilomycin A1 incubation had no effect on the number of spontaneous [Ca2+]i oscillations indicating that they were not dependent on vesicular neurotransmitter release. Oscillations were also unaffected by ryanodine. Phospholipase C (PLC) inhibition decreased the number of astrocytes responding to metabotropic glutamate receptor (mGluR) activation but did not reduce the number of spontaneously active astrocytes, indicating that [Ca2+]i increases are not due to membrane-coupled PLC activation. Spontaneous [Ca2+]i increases were abolished by an IP3 receptor antagonist, whilst the protein kinase C (PKC) inhibitor chelerythrine chloride prolonged their duration, indicating a role for PKC and inositol 1,4,5,-triphosphate receptor activation. BayK8644 increased the number of astrocytes exhibiting [Ca2+]i oscillations, and prolonged the responses to mGluR activation, indicating a possible effect on store-operated Ca2+ entry. Increasing [Ca2+]o increased the number of spontaneously active astrocytes and the number of transients exhibited by each astrocyte. Inhibition of the endoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid also induced [Ca2+]i transients in astrocytes indicating a role for cytoplasmic Ca2+ in the induction of spontaneous oscillations. Incubation with 20 μM Fluo-4 reduced the number of astrocytes exhibiting spontaneous increases. This study indicates that Ca2+ has a role in triggering Ca2+ release from an inositol 1,4,5,-triphosphate sensitive store in astrocytes during the generation of spontaneous [Ca2+]i oscillations

Laser-induced breakdown spectroscopy quantitative analysis method via adaptive analytical line selection and relevance vector machine regression model

Abstract A new LIBS quantitative analysis method based on analytical line adaptive selection and Relevance Vector Machine (RVM) regression model is proposed. First, a scheme of adaptively selecting analytical line is put forward in order to overcome the drawback of high dependency on a priori knowledge. The candidate analytical lines are automatically selected based on the built-in characteristics of spectral lines, such as spectral intensity, wavelength and width at half height. The analytical lines which will be used as input variables of regression model are determined adaptively according to the samples for both training and testing. Second, an LIBS quantitative analysis method based on RVM is presented. The intensities of analytical lines and the elemental concentrations of certified standard samples are used to train the RVM regression model. The predicted elemental concentration analysis results will be given with a form of confidence interval of probabilistic distribution, which is helpful for evaluating the uncertainness contained in the measured spectra. Chromium concentration analysis experiments of 23 certified standard high-alloy steel samples have been carried out. The multiple correlation coefficient of the prediction was up to 98.85%, and the average relative error of the prediction was 4.01%. The experiment results showed that the proposed LIBS quantitative analysis method achieved better prediction accuracy and better modeling robustness compared with the methods based on partial least squares regression, artificial neural network and standard support vector machine.

Generation of optical frequency combs in fibres:an optical pulse analysis

The innovation of optical frequency combs (OFCs) generated in passive mode-locked lasers has provided astronomy with unprecedented accuracy for wavelength calibration in high-resolution spectroscopy in research areas such as the discovery of exoplanets or the measurement of fundamental constants. The unique properties of OCFs, namely a highly dense spectrum of uniformly spaced emission lines of nearly equal intensity over the nominal wavelength range, is not only beneficial for high-resolution spectroscopy. Also in the low- to medium-resolution domain, the OFCs hold the promise to revolutionise the calibration techniques. Here, we present a novel method for generation of OFCs. As opposed to the mode-locked laser-based approach that can be complex, costly, and difficult to stabilise, we propose an all optical fibre-based system that is simple, compact, stable, and low-cost. Our system consists of three optical fibres where the first one is a conventional single-mode fibre, the second one is an erbium-doped fibre and the third one is a highly nonlinear low-dispersion fibre. The system is pumped by two equally intense continuous-wave (CW) lasers. To be able to control the quality and the bandwidth of the OFCs, it is crucial to understand how optical solitons arise out of the initial modulated CW field in the first fibre. Here, we numerically investigate the pulse evolution in the first fibre using the technique of the solitons radiation beat analysis. Having applied this technique, we realised that formation of higherorder solitons is supported in the low-energy region, whereas, in the high-energy region, Kuznetsov-Ma solitons appear.

In vitro protective effect and antioxidant mechanism of Resveratrol induced by Dapsone Hydroxylamine in human cells

Dapsone (DDS) hydroxylamine metabolites cause oxidative stress- linked adverse effects in patients, such as methemoglobin formation and DNA damage. This study evaluated the ameliorating effect of the antioxidant resveratrol (RSV) on DDS hydroxylamine (DDSNHOH) mediated toxicity in vitro using human erythrocytes and lymphocytes. The antioxidant mechanism was also studied using in-silico methods. In addition, RSV provided intracellular protection by inhibiting DNA damage in human lymphocytes induced by DDS-NHOH. However, whilst pretreatment with RSV (10-1000 μM significantly attenuated DDS-NHOH-induced methemoglobinemia, but it was not only significantly less effective than methylene blue (MET), but also post-treatment with RSV did not reverse methemoglobin formation, contrarily to that observed with MET. DDS-NHOH inhibited catalase (CAT) activity and reactive oxygen species (ROS) generation, but did not alter superoxide dismutase (SOD) activity in erythrocytes. Pretreatment with RSV did not alter these antioxidant enzymes activities in erythrocytes treated with DDS-NHOH. Theoretical calculations using density functional theory methods showed that DDS-NHOH has a pro-oxidant effect, whereas RSV and MET have antioxidant effect on ROS. The effect on methemoglobinemia reversion for MET was significantly higher than that of RSV. These data suggest that the pretreatment with resveratrol may decrease heme-iron oxidation and DNA damage through reduction of ROS generated in cells during DDS therapy.

Generation of drifting optical pulses

The radiation in the form of Airy and Gaussian optical pulses is investigated. It is shown that the pulse envelope moves decelerating in the time-spatial coordinates on the surface of a parabolic cylinder for the Airy pulse and a hyperbolic cylinder for the Gaussian. © 2013 IEEE.

Improved response time of laser etched polymer optical fiber Bragg grating humidity sensor

The humidity sensor made of polymer optical fiber Bragg grating (POFBG) responds to the water content change in fiber induced by the change of environmental condition. The response time strongly depends on fiber size as the water change is a diffusion process. The ultra short laser pulses have been providing an effective micro fabrication method to achieve spatial localized modification in materials. In this work we used the excimer laser to create different microstructures (slot, D-shape) in POFBG to improve its performance. A significant improvement in the response time has been achieved in a laser etched D-shaped POFBG humidity sensor.

Temporal and spatio-temporal regimes of generation of Raman fibre lasers

Temporal dynamics of Raman fibre lasers tend to have very complex nature, owing to great cavity lengths and high nonlinearity, being stochastic on short time scales and quasi-continuous on longer time scales. Generally fibre laser intensity dynamics is represented by one-dimensional time-series, which in case of quasi-continuous wave generation in Raman fibre lasers gives little insight into the processes underlying the operation of a laser. New methods of analysis and data representation could help to uncover the underlying physical processes, understand the dynamics or improve the performance of the system. Using intrinsic periodicity of laser radiation, one dimensional intensity time series of a Raman fibre laser was analysed over fast and slow variation time. This allowed to experimentally observe various spatio-temporal regimes of generation, such as laminar, turbulent, partial mode-lock, as well as transitions between them and identify the mechanisms responsible for the transitions. Great cavity length and high nonlinearity also make it difficult to achieve stable high repetition rate mode-locking in Raman fibre lasers. Using Faraday parametric instability in extremely simple linear cavity experimental configuration, a very high order harmonic mode-locking was achieved in ò.ò kmlong Raman fibre laser. The maximum achieved pulse repetition rate was 12 GHz, with 7.3 ps long Gaussian shaped pulses. There is a new type of random lasers – random distributed feedback Raman fibre laser, which temporal properties cannot be controlled by conventionalmode-locking or Q-switch techniques and mechanisms. By adjusting the pump configuration, a very stable pulsed operation of random distributed feedback Raman fibre laser was achieved. Pulse duration varied in the range from 50 to 200 μs depending on the pump power and the cavity length. Pulse repetition rate scaling on the parameters of the system was experimentally identified.

Generation of harmonic oscillations in ring resonator with high Q-factor

We report on generation of harmonic oscillations with frequencies of hundreds of MHz and radio-frequency linewidth of 13 Hz in unidirectional ring laser oscillator. This high stability makes these oscillators a suitable substitute for existing quartz resonators used in high frequency optoelectronics applications.