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KEY POINTS: Although optogenetics has clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies lack the capability to react acutely to ongoing cardiac wave dynamics. Here, we developed an all-optical platform to monitor and control electrical activity in real-time. The methodology was applied to restore normal electrical activity after atrioventricular block and to manipulate the intraventricular propagation of the electrical wavefront. The closed-loop approach was also applied to simulate a re-entrant circuit across the ventricle. The development of this innovative optical methodology provides the first proof-of-concept that a real-time all-optical stimulation can control cardiac rhythm in normal and abnormal conditions. ABSTRACT: Optogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all-optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide-field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free-run mode with submillisecond temporal resolution or in a closed-loop fashion: a tailored hardware and software platform allowed real-time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real-time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real-time resynchronization therapy and cardiac defibrillation. Furthermore, the closed-loop approach was applied to simulate a re-entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof-of-concept that a real-time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart.
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Arritmias Cardíacas/terapia , Bloqueo Atrioventricular/terapia , Terapia por Estimulación Eléctrica/métodos , Atrios Cardíacos/citología , Ventrículos Cardíacos/citología , Optogenética/instrumentación , Potenciales de Acción , Animales , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Bloqueo Atrioventricular/genética , Bloqueo Atrioventricular/fisiopatología , Técnicas Electrofisiológicas Cardíacas , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/efectos de la radiación , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/efectos de la radiación , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Imagen ÓpticaRESUMEN
BACKGROUND: Electric and magnetic fields (EMF) might be involved in human disease and numerous research and scientific reviews have been conducted to address this question. In particular thyroid structural and functional alterations caused by various forms of non-ionizing radiation have been described. AIM: The aim of this study was to analyze the possible effects of EMF on thyroid, in particular we analyzed the effects caused by a GSM (Global System for Mobile Communications) signal (900 MHz) on cultured thyroid cells (FRTL- 5). MATERIAL AND METHODS: The experimental setup was designed in order to expose samples to a radiofrequency wave in well-controlled conditions. We used the FRTL-5 cell line, an epithelial monoclonal continuous cell line derived from Fisher rat thyroid tissue growing as monolayer, expressing the TSH receptor and the sodium-iodide symporter (NIS). FRTL-5 were subsequently irradiate for 24, 48, and 96 h with EMF (800-900 MHz, power-frequency of mobile communication systems) and iodide uptake and cAMP production were measured. RESULTS: The irradiation of cells with EMF at 900 Mhz for 24, 48, and 96 h did not influence the level of cAMP production and was not able to modify iodide accumulation in FRTL- 5 cells with respect to basal conditions. CONCLUSIONS: In conclusion, EMF do not seem to be able to interfere with the biochemical properties of FRTL-5 cells in vitro.
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Línea Celular/efectos de la radiación , Campos Electromagnéticos , Animales , Línea Celular/metabolismo , AMP Cíclico/metabolismo , Relación Dosis-Respuesta en la Radiación , Humanos , Yoduros/metabolismo , Masculino , Ratas , Glándula Tiroides/citología , Glándula Tiroides/efectos de la radiaciónRESUMEN
Time-Of-Flight (TOF) methods are very effective to detect particles accelerated in laser-plasma interactions, but they show significant limitations when used in experiments with high energy and intensity lasers, where both high-energy ions and remarkable levels of ElectroMagnetic Pulses (EMPs) in the radiofrequency-microwave range are generated. Here we describe a novel advanced diagnostic method for the characterization of protons accelerated by intense matter interactions with high-energy and high-intensity ultra-short laser pulses up to the femtosecond and even future attosecond range. The method employs a stacked diamond detector structure and the TOF technique, featuring high sensitivity, high resolution, high radiation hardness and high signal-to-noise ratio in environments heavily affected by remarkable EMP fields. A detailed study on the use, the optimization and the properties of a single module of the stack is here described for an experiment where a fast diamond detector is employed in an highly EMP-polluted environment. Accurate calibrated spectra of accelerated protons are presented from an experiment with the femtosecond Flame laser (beyond 100 TW power and ~ 1019 W/cm2 intensity) interacting with thin foil targets. The results can be readily applied to the case of complex stack configurations and to more general experimental conditions.
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We use optical interferometry to study the propagation of femtosecond laser pulses in gases. We show the measurements of propagation in a nitrogen gas jet and we compare the results with propagation in He under the same irradiation conditions. We find that in the case of nitrogen, the detailed temporal structure of the laser pulse can be tracked and visualized by measuring the phase and the resulting electron-density map. A dramatically different behavior occurs in He gas jets, where no details of the temporal structure of the laser pulse are visible. These observations are explained in terms of the ionization dynamics of nitrogen compared to helium. These circumstances make N2 gas sensitive to variations in the electric field and, therefore, allow the laser-pulse temporal and spatial structures to be visualized in detail.
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Spectrally resolved two-dimensional imaging of ultrashort laser-produced plasmas is described, obtained by means of an advanced technique. The technique has been tested with microplasmas produced by ultrashort relativistic laser pulses. The technique is based on the use of a pinhole camera equipped with a charge coupled device detector operating in the single-photon regime. The spectral resolution is about 150 eV in the 4-10 keV range, and images in any selected photon energy range have a spatial resolution of 5 microm. The potential of the technique to study fast electron propagation in ultraintense laser interaction with multilayer targets is discussed and some preliminary results are shown.
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Gases/análisis , Gases/química , Aumento de la Imagen/instrumentación , Interpretación de Imagen Asistida por Computador/instrumentación , Rayos Láser , Procesamiento de Señales Asistido por Computador/instrumentación , Espectrometría por Rayos X/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Calor , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Reproducibilidad de los Resultados , Semiconductores , Sensibilidad y Especificidad , Espectrometría por Rayos X/métodosRESUMEN
We use optical interferometry to investigate ultrafast ionization induced by an intense, ultrashort laser pulse propagating in a helium gas. Besides standard phase shift information, our interferograms show a localized region of fringe visibility depletion (FVD) that moves along the laser propagation axis at luminal velocity. We find that such a loss of visibility can be quantitatively explained by the ultrafast change of refractive index due to the field ionization of the gas in the laser pulse width. We demonstrate that by combining the post facto phase shift distribution with the probe pulse transit effect in the ionizing region, the analysis of the observed FVD yields significant information on the ultrafast dynamics of propagation of the ionization front in the gas.
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The interaction of an ultraintense, 30-fs laser pulse with a preformed plasma was investigated as a method of producing a beam of high-energy electrons. We used thin foil targets that are exploded by the laser amplified spontaneous emission preceding the main pulse. Optical diagnostics show that the main pulse interacts with a plasma whose density is well below the critical density. By varying the foil thickness, we were able to obtain a substantial emission of electrons in a narrow cone along the laser direction with a typical energy well above the laser ponderomotive potential. These results are explained in terms of wake-field acceleration.
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Spatially resolved K-shell spectroscopy is used here to investigate the interaction of an ultrashort laser pulse (λ=800 nm, τ=40 fs) with a Ti foil under intense irradiation (Iλ(2)=2×10(18)Wµm(2)cm(-2)) and the following fast electron generation and transport into the target. The effect of laser pulse polarization (p, s, and circular) on the Kα yield and line shape is probed. The radial structure of intensity and width of the lines, obtained by a discretized Abel deconvolution algorithm, suggests an annular distribution of both the hot electron propagation into the target and the target temperature. An accurate modeling of Kα line shapes was performed, revealing temperature gradients, going from a few eV up to 15-20 eV, depending on the pulse polarization. Results are discussed in terms of mechanisms of hot electron generation and of their transport through the preplasma in front of the target.
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Rayos Láser , Modelos Químicos , Gases em Plasma/química , Gases em Plasma/efectos de la radiación , Simulación por Computador , Rayos XRESUMEN
A gamma-ray source with an intense component around the giant dipole resonance for photonuclear absorption has been obtained via bremsstrahlung of electron bunches driven by a 10-TW tabletop laser. 3D particle-in-cell simulation proves the achievement of a nonlinear regime leading to efficient acceleration of several sequential electron bunches per each laser pulse. The rate of the gamma-ray yield in the giant dipole resonance region (8
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Laser plasma interferograms are currently analyzed by extraction of the phase-shift map with fast Fourier transform (FFT) techniques [Appl. Opt. 18, 3101 (1985)]. This methodology works well when interferograms are only marginally affected by noise and reduction of fringe visibility, but it can fail to produce accurate phase-shift maps when low-quality images are dealt with. We present a novel procedure for a phase-shift map computation that makes extensive use of the ridge extraction in the continuous wavelet transform (CWT) framework. The CWT tool is flexible because of the wide adaptability of the analyzing basis, and it can be accurate because of the intrinsic noise reduction in the ridge extraction. A comparative analysis of the accuracy performances of the new tool and the FFT-based one shows that the CWT-based tool produces phase maps considerably less noisy and that it can better resolve local inhomogeneties.